2k4e - Revision history

OCA at 19:10, 29 May 2024

2024-05-29T19:10:06Z

← Older revision		Revision as of 19:10, 29 May 2024
Line 1:		Line 1:

	==Solution structure of the HIV-2 UNMYRISTOYLATED MATRIX PROTEIN==		==Solution structure of the HIV-2 UNMYRISTOYLATED MATRIX PROTEIN==
	<StructureSection load='2k4e' size='340' side='right'caption='[[2k4e~~]], [[NMR_Ensembles_of_Models \| 20 NMR models~~]]' scene=''>		<StructureSection load='2k4e' size='340' side='right'caption='[[2k4e]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2k4e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Hiv-2 Hiv-~~2]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K4E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K4E FirstGlance]. <br>		<table><tr><td colspan='2'>[[2k4e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_type_2_(ISOLATE_ROD) Human immunodeficiency virus type 2 (ISOLATE ROD)]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K4E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K4E FirstGlance]. <br>
	</td></tr><tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~><div style='overflow: auto; max-height: 3em;'>[[2k4h\|2k4h]], [[2k4i\|2k4i]]</div></td></tr>~~		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
	~~<tr~~ id~~='gene'><td class~~="~~sblockLbl~~">~~<b>[[Gene\|Gene:]]</b></td><td class="sblockDat">gag-pol ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11720 HIV-2])~~</td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2k4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k4e OCA], [https://pdbe.org/2k4e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k4e RCSB], [https://www.ebi.ac.uk/pdbsum/2k4e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k4e ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2k4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k4e OCA], [https://pdbe.org/2k4e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k4e RCSB], [https://www.ebi.ac.uk/pdbsum/2k4e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k4e ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/POL_HV2RO POL_HV2RO]] Gag-Pol polyprotein and Gag polyprotein may regulate their own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, Gag-Pol and Gag would promote translation, whereas at high concentration, the polyproteins encapsidate genomic RNA and then shutt off translation (By similarity). Matrix protein p17 has two main functions: in infected cell, it targets Gag and Gag-pol polyproteins to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. The second function is to play a role in nuclear localization of the viral genome at the very start of cell infection. Matrix protein is the part of the pre-integration complex. The myristoylation signal and the NLS exert conflicting influences its subcellular localization. The key regulation of these motifs might be phosphorylation of a portion of MA molecules on the C-terminal tyrosine at the time of virus maturation, by virion-associated cellular tyrosine kinase. Implicated in the release from host cell mediated by Vpu (By similarity). Capsid protein p24 forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry. Interaction with human PPIA/CYPA protects the virus from restriction by human TRIM5-alpha and from an unknown antiviral activity in human cells. This capsid restriction by TRIM5 is one of the factors which restricts HIV to the human species (By similarity). Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers. Facilitates rearangement of nucleic acid secondary structure during retrotranscription of genomic RNA. This capability is referred to as nucleic acid chaperone activity (By similarity). The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell (By similarity). Reverse transcriptase/ribonuclease H (RT) is a multifunctional enzyme that converts the viral dimeric RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H can probably proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends (By similarity). Integrase catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration (By similarity).		[https://www.uniprot.org/uniprot/POL_HV2RO POL_HV2RO] Gag-Pol polyprotein and Gag polyprotein may regulate their own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, Gag-Pol and Gag would promote translation, whereas at high concentration, the polyproteins encapsidate genomic RNA and then shutt off translation (By similarity). Matrix protein p17 has two main functions: in infected cell, it targets Gag and Gag-pol polyproteins to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. The second function is to play a role in nuclear localization of the viral genome at the very start of cell infection. Matrix protein is the part of the pre-integration complex. The myristoylation signal and the NLS exert conflicting influences its subcellular localization. The key regulation of these motifs might be phosphorylation of a portion of MA molecules on the C-terminal tyrosine at the time of virus maturation, by virion-associated cellular tyrosine kinase. Implicated in the release from host cell mediated by Vpu (By similarity). Capsid protein p24 forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry. Interaction with human PPIA/CYPA protects the virus from restriction by human TRIM5-alpha and from an unknown antiviral activity in human cells. This capsid restriction by TRIM5 is one of the factors which restricts HIV to the human species (By similarity). Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers. Facilitates rearangement of nucleic acid secondary structure during retrotranscription of genomic RNA. This capability is referred to as nucleic acid chaperone activity (By similarity). The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell (By similarity). Reverse transcriptase/ribonuclease H (RT) is a multifunctional enzyme that converts the viral dimeric RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H can probably proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends (By similarity). Integrase catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration (By similarity).
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 33:		Line 32:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	~~[[Category: Hiv-2]]~~
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Ablan~~, S D~~]]		[[Category: Ablan SD]]
	[[Category: Andrews, K]]		[[Category: Andrews K]]
	[[Category: Freed~~, E O~~]]		[[Category: Freed EO]]
	[[Category: Ghanam~~, R H~~]]		[[Category: Ghanam RH]]
	[[Category: Kim, A]]		[[Category: Kim A]]
	[[Category: Nagashima, K]]		[[Category: Nagashima K]]
	[[Category: Saad~~, J S~~]]		[[Category: Saad JS]]
	[[Category: Summers~~, M F]]~~		[[Category: Summers MF]]
	~~[[Category: Aid]]~~
	~~[[Category: Capsid protein]]~~
	~~[[Category: Gag]]~~
	~~[[Category: Hiv]]~~
	~~[[Category: Matrix]]~~
	~~[[Category: Myristate]]~~
	~~[[Category: Plasma membrane]]~~
	~~[[Category: Structural protein]]~~
	~~[[Category: Virion~~]]

OCA at 08:09, 7 April 2021

2021-04-07T08:09:15Z

← Older revision		Revision as of 08:09, 7 April 2021
Line 1:		Line 1:

	==Solution structure of the HIV-2 UNMYRISTOYLATED MATRIX PROTEIN==		==Solution structure of the HIV-2 UNMYRISTOYLATED MATRIX PROTEIN==
	<StructureSection load='2k4e' size='340' side='right' caption='[[2k4e]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>		<StructureSection load='2k4e' size='340' side='right'caption='[[2k4e]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2k4e]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Hiv-2 Hiv-2]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K4E OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2K4E FirstGlance]. <br>		<table><tr><td colspan='2'>[[2k4e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Hiv-2 Hiv-2]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K4E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K4E FirstGlance]. <br>
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2k4h\|2k4h]], [[2k4i\|2k4i]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2k4h\|2k4h]], [[2k4i\|2k4i]]</div></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">gag-pol ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11720 HIV-2])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">gag-pol ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11720 HIV-2])</td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2k4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k4e OCA], [~~http~~://pdbe.org/2k4e PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2k4e RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2k4e PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2k4e ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2k4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k4e OCA], [https://pdbe.org/2k4e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k4e RCSB], [https://www.ebi.ac.uk/pdbsum/2k4e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k4e ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/POL_HV2RO POL_HV2RO]] Gag-Pol polyprotein and Gag polyprotein may regulate their own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, Gag-Pol and Gag would promote translation, whereas at high concentration, the polyproteins encapsidate genomic RNA and then shutt off translation (By similarity). Matrix protein p17 has two main functions: in infected cell, it targets Gag and Gag-pol polyproteins to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. The second function is to play a role in nuclear localization of the viral genome at the very start of cell infection. Matrix protein is the part of the pre-integration complex. The myristoylation signal and the NLS exert conflicting influences its subcellular localization. The key regulation of these motifs might be phosphorylation of a portion of MA molecules on the C-terminal tyrosine at the time of virus maturation, by virion-associated cellular tyrosine kinase. Implicated in the release from host cell mediated by Vpu (By similarity). Capsid protein p24 forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry. Interaction with human PPIA/CYPA protects the virus from restriction by human TRIM5-alpha and from an unknown antiviral activity in human cells. This capsid restriction by TRIM5 is one of the factors which restricts HIV to the human species (By similarity). Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers. Facilitates rearangement of nucleic acid secondary structure during retrotranscription of genomic RNA. This capability is referred to as nucleic acid chaperone activity (By similarity). The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell (By similarity). Reverse transcriptase/ribonuclease H (RT) is a multifunctional enzyme that converts the viral dimeric RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H can probably proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends (By similarity). Integrase catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration (By similarity).		[[https://www.uniprot.org/uniprot/POL_HV2RO POL_HV2RO]] Gag-Pol polyprotein and Gag polyprotein may regulate their own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, Gag-Pol and Gag would promote translation, whereas at high concentration, the polyproteins encapsidate genomic RNA and then shutt off translation (By similarity). Matrix protein p17 has two main functions: in infected cell, it targets Gag and Gag-pol polyproteins to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. The second function is to play a role in nuclear localization of the viral genome at the very start of cell infection. Matrix protein is the part of the pre-integration complex. The myristoylation signal and the NLS exert conflicting influences its subcellular localization. The key regulation of these motifs might be phosphorylation of a portion of MA molecules on the C-terminal tyrosine at the time of virus maturation, by virion-associated cellular tyrosine kinase. Implicated in the release from host cell mediated by Vpu (By similarity). Capsid protein p24 forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry. Interaction with human PPIA/CYPA protects the virus from restriction by human TRIM5-alpha and from an unknown antiviral activity in human cells. This capsid restriction by TRIM5 is one of the factors which restricts HIV to the human species (By similarity). Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers. Facilitates rearangement of nucleic acid secondary structure during retrotranscription of genomic RNA. This capability is referred to as nucleic acid chaperone activity (By similarity). The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell (By similarity). Reverse transcriptase/ribonuclease H (RT) is a multifunctional enzyme that converts the viral dimeric RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H can probably proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends (By similarity). Integrase catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration (By similarity).
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 34:		Line 34:
	</StructureSection>		</StructureSection>
	[[Category: Hiv-2]]		[[Category: Hiv-2]]
			[[Category: Large Structures]]
	[[Category: Ablan, S D]]		[[Category: Ablan, S D]]
	[[Category: Andrews, K]]		[[Category: Andrews, K]]

OCA at 11:09, 18 July 2018

2018-07-18T11:09:48Z

← Older revision		Revision as of 11:09, 18 July 2018
Line 1:		Line 1:

	==Solution structure of the HIV-2 UNMYRISTOYLATED MATRIX PROTEIN==		==Solution structure of the HIV-2 UNMYRISTOYLATED MATRIX PROTEIN==
	<StructureSection load='2k4e' size='340' side='right' caption='[[2k4e]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>		<StructureSection load='2k4e' size='340' side='right' caption='[[2k4e]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2k4h\|2k4h]], [[2k4i\|2k4i]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2k4h\|2k4h]], [[2k4i\|2k4i]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">gag-pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11720 HIV-2])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">gag-pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11720 HIV-2])</td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2k4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k4e OCA], [http://pdbe.org/2k4e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2k4e RCSB], [http://www.ebi.ac.uk/pdbsum/2k4e PDBsum]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2k4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k4e OCA], [http://pdbe.org/2k4e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2k4e RCSB], [http://www.ebi.ac.uk/pdbsum/2k4e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2k4e ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 13:		Line 14:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k4/2k4e_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k4/2k4e_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2k4e ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 07:13, 11 September 2015

2015-09-11T07:13:20Z

← Older revision		Revision as of 07:13, 11 September 2015
Line 2:		Line 2:
	<StructureSection load='2k4e' size='340' side='right' caption='[[2k4e]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>		<StructureSection load='2k4e' size='340' side='right' caption='[[2k4e]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2k4e]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Human_immunodeficiency_virus_2 Human immunodeficiency virus~~ 2]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K4E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2K4E FirstGlance]. <br>		<table><tr><td colspan='2'>[[2k4e]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Hiv-2 Hiv-2]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K4E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2K4E FirstGlance]. <br>
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2k4h\|2k4h]], [[2k4i\|2k4i]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2k4h\|2k4h]], [[2k4i\|2k4i]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">gag-pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=~~11709 Human immunodeficiency virus~~ 2])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">gag-pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11720 HIV-2])</td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2k4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k4e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2k4e RCSB], [http://www.ebi.ac.uk/pdbsum/2k4e PDBsum]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2k4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k4e OCA], [http://pdbe.org/2k4e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2k4e RCSB], [http://www.ebi.ac.uk/pdbsum/2k4e PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 27:		Line 27:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
			<div class="pdbe-citations 2k4e" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human immunodeficiency virus~~ 2]]		[[Category: Hiv-2]]
	[[Category: Ablan, S D]]		[[Category: Ablan, S D]]
	[[Category: Andrews, K]]		[[Category: Andrews, K]]

OCA at 13:05, 25 December 2014

2014-12-25T13:05:02Z

← Older revision		Revision as of 13:05, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2k4e]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_2 Human immunodeficiency virus 2]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K4E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2K4E FirstGlance]. <br>		<table><tr><td colspan='2'>[[2k4e]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_2 Human immunodeficiency virus 2]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K4E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2K4E FirstGlance]. <br>
	</td></tr><tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2k4h\|2k4h]], [[2k4i\|2k4i]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2k4h\|2k4h]], [[2k4i\|2k4i]]</td></tr>
	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">gag-pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11709 Human immunodeficiency virus 2])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">gag-pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11709 Human immunodeficiency virus 2])</td></tr>
	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2k4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k4e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2k4e RCSB], [http://www.ebi.ac.uk/pdbsum/2k4e PDBsum]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2k4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k4e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2k4e RCSB], [http://www.ebi.ac.uk/pdbsum/2k4e PDBsum]</span></td></tr>
	<table>		</table>
			== Function ==
			[[http://www.uniprot.org/uniprot/POL_HV2RO POL_HV2RO]] Gag-Pol polyprotein and Gag polyprotein may regulate their own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, Gag-Pol and Gag would promote translation, whereas at high concentration, the polyproteins encapsidate genomic RNA and then shutt off translation (By similarity). Matrix protein p17 has two main functions: in infected cell, it targets Gag and Gag-pol polyproteins to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. The second function is to play a role in nuclear localization of the viral genome at the very start of cell infection. Matrix protein is the part of the pre-integration complex. The myristoylation signal and the NLS exert conflicting influences its subcellular localization. The key regulation of these motifs might be phosphorylation of a portion of MA molecules on the C-terminal tyrosine at the time of virus maturation, by virion-associated cellular tyrosine kinase. Implicated in the release from host cell mediated by Vpu (By similarity). Capsid protein p24 forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry. Interaction with human PPIA/CYPA protects the virus from restriction by human TRIM5-alpha and from an unknown antiviral activity in human cells. This capsid restriction by TRIM5 is one of the factors which restricts HIV to the human species (By similarity). Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers. Facilitates rearangement of nucleic acid secondary structure during retrotranscription of genomic RNA. This capability is referred to as nucleic acid chaperone activity (By similarity). The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell (By similarity). Reverse transcriptase/ribonuclease H (RT) is a multifunctional enzyme that converts the viral dimeric RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H can probably proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends (By similarity). Integrase catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration (By similarity).
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 30:		Line 32:
	</StructureSection>		</StructureSection>
	[[Category: Human immunodeficiency virus 2]]		[[Category: Human immunodeficiency virus 2]]
	[[Category: Ablan, S D.]]		[[Category: Ablan, S D]]
	[[Category: Andrews, K.]]		[[Category: Andrews, K]]
	[[Category: Freed, E O.]]		[[Category: Freed, E O]]
	[[Category: Ghanam, R H.]]		[[Category: Ghanam, R H]]
	[[Category: Kim, A.]]		[[Category: Kim, A]]
	[[Category: Nagashima, K.]]		[[Category: Nagashima, K]]
	[[Category: Saad, J S.]]		[[Category: Saad, J S]]
	[[Category: Summers, M F.]]		[[Category: Summers, M F]]
	[[Category: Aid]]		[[Category: Aid]]
	[[Category: Capsid protein]]		[[Category: Capsid protein]]

OCA at 10:51, 30 September 2014

2014-09-30T10:51:25Z

← Older revision		Revision as of 10:51, 30 September 2014
Line 1:		Line 1:
	[[Image:~~2k4e~~.~~png~~\|~~left~~\|~~200px~~]]		==Solution structure of the HIV-2 UNMYRISTOYLATED MATRIX PROTEIN==
			<StructureSection load='2k4e' size='340' side='right' caption='[[2k4e]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[2k4e]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_2 Human immunodeficiency virus 2]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K4E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2K4E FirstGlance]. <br>
			</td></tr><tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2k4h\|2k4h]], [[2k4i\|2k4i]]</td></tr>
			<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">gag-pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11709 Human immunodeficiency virus 2])</td></tr>
			<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2k4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k4e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2k4e RCSB], [http://www.ebi.ac.uk/pdbsum/2k4e PDBsum]</span></td></tr>
			<table>
			== Evolutionary Conservation ==
			[[Image:Consurf_key_small.gif\|200px\|right]]
			Check<jmol>
			<jmolCheckbox>
			<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k4/2k4e_consurf.spt"</scriptWhenChecked>
			<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
			<text>to colour the structure by Evolutionary Conservation</text>
			</jmolCheckbox>
			</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
			<div style="clear:both"></div>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			During the late phase of retroviral replication, newly synthesized Gag proteins are targeted to the plasma membrane (PM), where they assemble and bud to form immature virus particles. Membrane targeting by human immunodeficiency virus type 1 (HIV-1) Gag is mediated by the PM marker molecule phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P(2)], which is capable of binding to the matrix (MA) domain of Gag in an extended lipid conformation and of triggering myristate exposure. Here, we show that, as observed previously for HIV-1 MA, the myristyl group of HIV-2 MA is partially sequestered within a narrow hydrophobic tunnel formed by side chains of helices 1, 2, 3, and 5. However, the myristate of HIV-2 MA is more tightly sequestered than that of the HIV-1 protein and does not exhibit concentration-dependent exposure. Soluble PI(4,5)P(2) analogs containing truncated acyl chains bind HIV-2 MA and induce minor long-range structural changes but do not trigger myristate exposure. Despite these differences, the site of HIV-2 assembly in vivo can be manipulated by enzymes that regulate PI(4,5)P(2) localization. Our findings indicate that HIV-1 and HIV-2 are both targeted to the PM for assembly via a PI(4,5)P(2)-dependent mechanism, despite differences in the sensitivity of the MA myristyl switch, and suggest a potential mechanism that may contribute to the poor replication kinetics of HIV-2.

	~~{{STRUCTURE_2k4e\| PDB=2k4e \| SCENE= }}~~		Structure of the myristylated human immunodeficiency virus type 2 matrix protein and the role of phosphatidylinositol-(4,5)-bisphosphate in membrane targeting.,Saad JS, Ablan SD, Ghanam RH, Kim A, Andrews K, Nagashima K, Soheilian F, Freed EO, Summers MF J Mol Biol. 2008 Oct 3;382(2):434-47. Epub 2008 Jul 16. PMID:18657545<ref>PMID:18657545</ref>

	~~===Solution structure~~ of the ~~HIV-2 UNMYRISTOYLATED MATRIX PROTEIN===~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
	~~{{ABSTRACT_PUBMED_18657545}}~~		== References ==
			<references/>
	~~==About this Structure==~~		__TOC__
	~~[[2k4e]] is a 1 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Human_immunodeficiency_virus_2 Human immunodeficiency virus 2]~~. ~~Full experimental information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=2K4E OCA].~~		</StructureSection>

	==~~Reference~~==
	<~~ref group="xtra">PMID:018657545<~~/~~ref~~><~~references group="xtra"~~/>
	[[Category: Human immunodeficiency virus 2]]		[[Category: Human immunodeficiency virus 2]]
	[[Category: Ablan, S D.]]		[[Category: Ablan, S D.]]

OCA: Protected "2k4e" [edit=sysop:move=sysop]

2013-01-07T12:38:39Z

Protected "2k4e" [edit=sysop:move=sysop]

← Older revision	Revision as of 12:38, 7 January 2013
(No difference)

OCA at 12:38, 7 January 2013

2013-01-07T12:38:36Z

← Older revision		Revision as of 12:38, 7 January 2013
Line 1:		Line 1:
	~~{{Seed}}~~
	[[Image:2k4e.png\|left\|200px]]		[[Image:2k4e.png\|left\|200px]]

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_2k4e", creates the "Structure Box" on the page.~~
	~~You may change the PDB parameter (which sets the PDB file loaded into the applet)~~
	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded),~~
	~~or leave the SCENE parameter empty for the default display.~~
	~~-->~~
	{{STRUCTURE_2k4e\| PDB=2k4e \| SCENE= }}		{{STRUCTURE_2k4e\| PDB=2k4e \| SCENE= }}

	===Solution structure of the HIV-2 UNMYRISTOYLATED MATRIX PROTEIN===		===Solution structure of the HIV-2 UNMYRISTOYLATED MATRIX PROTEIN===


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	{{ABSTRACT_PUBMED_18657545}}		{{ABSTRACT_PUBMED_18657545}}

	==About this Structure==		==About this Structure==
	~~2K4E~~ is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_2 Human immunodeficiency virus 2]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K4E OCA].		[[2k4e]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_2 Human immunodeficiency virus 2]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K4E OCA].

	==Reference==		==Reference==
	<ref group="xtra">PMID:~~18657545~~</ref><references group="xtra"/>		<ref group="xtra">PMID:018657545</ref><references group="xtra"/>
	[[Category: Human immunodeficiency virus 2]]		[[Category: Human immunodeficiency virus 2]]
	[[Category: Ablan, S D.]]		[[Category: Ablan, S D.]]
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	[[Category: Matrix]]		[[Category: Matrix]]
	[[Category: Myristate]]		[[Category: Myristate]]
	~~[[Category: Nmr]]~~
	[[Category: Plasma membrane]]		[[Category: Plasma membrane]]
	[[Category: Structural protein]]		[[Category: Structural protein]]
	[[Category: Virion]]		[[Category: Virion]]

	~~''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 16:56:01 2009''~~

OCA at 14:56, 17 February 2009

2009-02-17T14:56:01Z

← Older revision		Revision as of 14:56, 17 February 2009
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	==About this Structure==		==About this Structure==
	2K4E is a ~~[[Single protein]]~~ structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_2 Human immunodeficiency virus 2]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K4E OCA].		2K4E is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_2 Human immunodeficiency virus 2]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K4E OCA].

	==Reference==		==Reference==
	Structure of the Myristylated Human Immunodeficiency Virus Type 2 Matrix Protein and the Role of Phosphatidylinositol-(4,5)-Bisphosphate in Membrane Targeting., Saad JS, Ablan SD, Ghanam RH, Kim A, Andrews K, Nagashima K, Soheilian F, Freed EO, Summers MF, J Mol Biol. 2008 Jul 16. PMID:~~[http://www.ncbi.nlm.nih.gov~~/~~pubmed~~/~~18657545 18657545]~~		<ref group="xtra">PMID:18657545</ref><references group="xtra"/>
	[[Category: Human immunodeficiency virus 2]]		[[Category: Human immunodeficiency virus 2]]
	~~[[Category: Single protein]]~~
	[[Category: Ablan, S D.]]		[[Category: Ablan, S D.]]
	[[Category: Andrews, K.]]		[[Category: Andrews, K.]]
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	[[Category: Virion]]		[[Category: Virion]]

	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Wed Sep~~ 17 12:59:~~42 2008~~''		''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 16:56:01 2009''

OCA at 09:59, 17 September 2008

2008-09-17T09:59:43Z

← Older revision		Revision as of 09:59, 17 September 2008
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	{{Seed}}		{{Seed}}
	[[Image:2k4e.~~jpg~~\|left\|200px]]		[[Image:2k4e.png\|left\|200px]]

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	[[Category: Virion]]		[[Category: Virion]]

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