View source for 6voy


==Cryo-EM structure of HTLV-1 instasome==
<StructureSection load='6voy' size='340' side='right'caption='[[6voy]], [[Resolution|resolution]] 3.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6voy]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Human_T-cell_leukemia_virus_type_I Human T-cell leukemia virus type I] and [https://en.wikipedia.org/wiki/Saccharolobus_solfataricus_P2 Saccharolobus solfataricus P2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VOY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VOY FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=6voy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6voy OCA], [https://pdbe.org/6voy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6voy RCSB], [https://www.ebi.ac.uk/pdbsum/6voy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6voy ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/POL_HTL1C POL_HTL1C] The matrix domain targets Gag, Gag-Pro and Gag-Pro-Pol polyproteins to the plasma membrane via a multipartite membrane binding signal, that includes its myristoylated N-terminus.[UniProtKB:P03345]  Matrix protein.[UniProtKB:P03345]  Forms the spherical core of the virus that encapsulates the genomic RNA-nucleocapsid complex.[UniProtKB:P03362]  Binds strongly to viral nucleic acids and promote their aggregation. Also destabilizes the nucleic acids duplexes via highly structured zinc-binding motifs.[UniProtKB:P03345]  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 (Potential). Cleaves the translation initiation factor eIF4G leading to the inhibition of host cap-dependent translation (By similarity).[UniProtKB:P03362][PROSITE-ProRule:PRU00275]  RT is a multifunctional enzyme that converts the viral 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-Pro 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 a polypurine tract (PPT) situated at the 5' end of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can 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 PPT that has not been removed by RNase H as primer. PPT 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).  RT is a multifunctional enzyme that converts the viral 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-Pro 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 a polypurine tract (PPT) situated at the 5' end of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can 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 PPT that has not been removed by RNase H as primer. PPT 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).  Catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions.[UniProtKB:P03362][https://www.uniprot.org/uniprot/DN7D_SACS2 DN7D_SACS2] Can constrain negative DNA supercoils. May be involved in maintaining the integrity of the genome at high temperature (By similarity). Stimulates the Holliday junction cleavage activity of Hjc (PubMed:11709558).[UniProtKB:P61990]<ref>PMID:11709558</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Integration of the reverse-transcribed viral DNA into host chromosomes is a critical step in the life-cycle of retroviruses, including an oncogenic delta(delta)-retrovirus human T-cell leukemia virus type-1 (HTLV-1). Retroviral integrase forms a higher order nucleoprotein assembly (intasome) to catalyze the integration reaction, in which the roles of host factors remain poorly understood. Here, we use cryo-electron microscopy to visualize the HTLV-1 intasome at 3.7-A resolution. The structure together with functional analyses reveal that the B56gamma (B'gamma) subunit of an essential host enzyme, protein phosphatase 2 A (PP2A), is repurposed as an integral component of the intasome to mediate HTLV-1 integration. Our studies reveal a key host-virus interaction underlying the replication of an important human pathogen and highlight divergent integration strategies of retroviruses.

Structural basis of host protein hijacking in human T-cell leukemia virus integration.,Bhatt V, Shi K, Salamango DJ, Moeller NH, Pandey KK, Bera S, Bohl TE, Kurniawan F, Orellana K, Zhang W, Grandgenett DP, Harris RS, Sundborger-Lunna AC, Aihara H Nat Commun. 2020 Jun 19;11(1):3121. doi: 10.1038/s41467-020-16963-6. PMID:32561747<ref>PMID:32561747</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6voy" style="background-color:#fffaf0;"></div>

==See Also==
*[[Protein phosphatase 3D structures|Protein phosphatase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Human T-cell leukemia virus type I]]
[[Category: Large Structures]]
[[Category: Saccharolobus solfataricus P2]]
[[Category: Aihara H]]
[[Category: Bhatt V]]
[[Category: Shi K]]
[[Category: Sundborger A]]