2bgr - Revision history

OCA at 13:36, 13 December 2023

2023-12-13T13:36:31Z

← Older revision		Revision as of 13:36, 13 December 2023
Line 3:		Line 3:
	<StructureSection load='2bgr' size='340' side='right'caption='[[2bgr]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='2bgr' size='340' side='right'caption='[[2bgr]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2bgr]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human ~~Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BGR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BGR FirstGlance]. <br>		<table><tr><td colspan='2'>[[2bgr]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BGR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BGR FirstGlance]. <br>
	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=BMA:BETA~~-~~D-MANNOSE'>BMA</scene>~~, ~~<scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>~~</td></tr>		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2Å</td></tr>
	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><~~div style~~='~~overflow~~: ~~auto; max~~-~~height: 3em;~~'>~~[[1j2e\|1j2e]], [[1n1m\|1n1m]], [[1nu6\|1nu6]], [[1nu8\|1nu8]], [[1pfq\|1pfq]], [[1r9m\|1r9m]], [[1rwq\|1rwq]], [[1tk3\|1tk3]], [[1tkr\|1tkr]], [[1u8e\|1u8e]], [[1w1i\|1w1i]], [[2bgn\|2bgn]]~~</~~div~~><~~/td></tr>~~		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b~~></td><~~td class~~=~~"sblockDat"><span class~~=~~'plainlinks'>[https~~:~~//en.wikipedia.org/wiki/Dipeptidyl~~-~~peptidase_IV Dipeptidyl~~-~~peptidase IV], with EC number [https://www.brenda~~-~~enzymes.info/php/result_flat.php4?ecno=3.4.14.5 3.4.14.5]~~ </~~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=2bgr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bgr OCA], [https://pdbe.org/2bgr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bgr RCSB], [https://www.ebi.ac.uk/pdbsum/2bgr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bgr 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=2bgr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bgr OCA], [https://pdbe.org/2bgr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bgr RCSB], [https://www.ebi.ac.uk/pdbsum/2bgr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bgr ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/DPP4_HUMAN DPP4_HUMAN]] Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion. In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation. When overexpressed, enhanced cell proliferation, a process inhibited by GPC3. Acts also as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline.<ref>PMID:10951221</ref> <ref>PMID:17549790</ref> <ref>PMID:10570924</ref> <ref>PMID:10900005</ref> <ref>PMID:11772392</ref> <ref>PMID:14691230</ref> <ref>PMID:16651416</ref> <ref>PMID:17287217</ref> <ref>PMID:18708048</ref> [[https://www.uniprot.org/uniprot/TAT_HV1Z2 TAT_HV1Z2]] Nuclear transcriptional activator of viral gene expression, that is essential for viral transcription from the LTR promoter and replication. Acts as a sequence-specific molecular adapter, directing components of the cellular transcription machinery to the viral RNA to promote processive transcription elongation by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. In the absence of Tat, the RNA Pol II generates short or non-processive transcripts that terminate at approximately 60 bp from the initiation site. Tat associates with the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. This binding increases Tat's affinity for a hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA) and allows Tat/P-TEFb complex to bind cooperatively to TAR RNA. The CDK9 component of P-TEFb and other Tat-activated kinases hyperphosphorylate the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B. In this purpose, it activates EIF2AK2/PKR which, in turns, may phosphorylate and target to degradation the inhibitor IkappaB-alpha which normally retains NF-kappa-B in the cytoplasm of unstimulated cells. Through its interaction with TBP, Tat may be involved in transcription initiation as well. Interacts with the cellular capping enzyme RNGTT to mediate co-transcriptional capping of viral mRNAs. Tat protein exerts as well a positive feedback on the translation of its cognate mRNA. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter. In the cytoplasm, Tat is thought to act as a translational activator of HIV-1 mRNAs (By similarity). Extracellular circulating Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as CD26, CXCR4, heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Endosomal low pH allows Tat to cross the endosome membrane to enter the cytosol and eventually further translocate into the nucleus, thereby inducing severe cell dysfunctions ranging from cell activation to cell death. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Tat seems to inhibit the HAT activity of KAT5/Tip60 and TAF1, and consequently modify the expression of specific cellular genes. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines (such as IL10) or cytokine receptors. May be involved in the derepression of host interleukin IL2 expression. Mediates the activation of cyclin-dependent kinases and dysregulation of microtubule network. Tat plays a role in T-cell and neurons apoptosis. Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Host extracellular matrix metalloproteinase MMP1 cleaves Tat and decreases Tat's mediated neurotoxicity. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. Binds to KDR/VEGFR-2. All these Tat-mediated effects enhance angiogenesis in Kaposi's sarcoma lesions (By similarity).		[https://www.uniprot.org/uniprot/DPP4_HUMAN DPP4_HUMAN] Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion. In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation. When overexpressed, enhanced cell proliferation, a process inhibited by GPC3. Acts also as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline.<ref>PMID:10951221</ref> <ref>PMID:17549790</ref> <ref>PMID:10570924</ref> <ref>PMID:10900005</ref> <ref>PMID:11772392</ref> <ref>PMID:14691230</ref> <ref>PMID:16651416</ref> <ref>PMID:17287217</ref> <ref>PMID:18708048</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Dipeptidyl-peptidase IV~~]]		[[Category: Homo sapiens]]
	[[Category: Human]]		[[Category: Human immunodeficiency virus 1]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Fan, H]]		[[Category: Fan H]]
	[[Category: Liu, J]]		[[Category: Liu J]]
	[[Category: Reutter, W]]		[[Category: Reutter W]]
	[[Category: Saenger, W]]		[[Category: Saenger W]]
	[[Category: Weihofen~~, W A]]~~		[[Category: Weihofen WA]]
	~~[[Category: Alpha/beta-hydrolase fold]]~~
	~~[[Category: Beta-propeller fold]]~~
	~~[[Category: Dppiv]]~~
	~~[[Category: Hydrolase]]~~
	~~[[Category: Hydrolase-complex~~]]

OCA at 13:09, 24 November 2021

2021-11-24T13:09:37Z

← Older revision		Revision as of 13:09, 24 November 2021
Line 3:		Line 3:
	<StructureSection load='2bgr' size='340' side='right'caption='[[2bgr]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='2bgr' size='340' side='right'caption='[[2bgr]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2bgr]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BGR OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2BGR FirstGlance]. <br>		<table><tr><td colspan='2'>[[2bgr]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BGR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BGR FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=~~FUC~~:~~ALPHA~~-L-~~FUCOSE~~'>~~FUC~~</scene>, <scene name='pdbligand=~~NAG~~:N-~~ACETYL~~-~~D-GLUCOSAMINE~~'>~~NAG~~</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1j2e\|1j2e]], [[1n1m\|1n1m]], [[1nu6\|1nu6]], [[1nu8\|1nu8]], [[1pfq\|1pfq]], [[1r9m\|1r9m]], [[1rwq\|1rwq]], [[1tk3\|1tk3]], [[1tkr\|1tkr]], [[1u8e\|1u8e]], [[1w1i\|1w1i]], [[2bgn\|2bgn]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1j2e\|1j2e]], [[1n1m\|1n1m]], [[1nu6\|1nu6]], [[1nu8\|1nu8]], [[1pfq\|1pfq]], [[1r9m\|1r9m]], [[1rwq\|1rwq]], [[1tk3\|1tk3]], [[1tkr\|1tkr]], [[1u8e\|1u8e]], [[1w1i\|1w1i]], [[2bgn\|2bgn]]</div></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Dipeptidyl-peptidase_IV Dipeptidyl-peptidase IV], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.5 3.4.14.5] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Dipeptidyl-peptidase_IV Dipeptidyl-peptidase IV], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.5 3.4.14.5] </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=2bgr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bgr OCA], [~~http~~://pdbe.org/2bgr PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2bgr RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2bgr PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2bgr 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=2bgr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bgr OCA], [https://pdbe.org/2bgr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bgr RCSB], [https://www.ebi.ac.uk/pdbsum/2bgr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bgr ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/DPP4_HUMAN DPP4_HUMAN]] Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion. In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation. When overexpressed, enhanced cell proliferation, a process inhibited by GPC3. Acts also as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline.<ref>PMID:10951221</ref> <ref>PMID:17549790</ref> <ref>PMID:10570924</ref> <ref>PMID:10900005</ref> <ref>PMID:11772392</ref> <ref>PMID:14691230</ref> <ref>PMID:16651416</ref> <ref>PMID:17287217</ref> <ref>PMID:18708048</ref> [[~~http~~://www.uniprot.org/uniprot/TAT_HV1Z2 TAT_HV1Z2]] Nuclear transcriptional activator of viral gene expression, that is essential for viral transcription from the LTR promoter and replication. Acts as a sequence-specific molecular adapter, directing components of the cellular transcription machinery to the viral RNA to promote processive transcription elongation by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. In the absence of Tat, the RNA Pol II generates short or non-processive transcripts that terminate at approximately 60 bp from the initiation site. Tat associates with the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. This binding increases Tat's affinity for a hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA) and allows Tat/P-TEFb complex to bind cooperatively to TAR RNA. The CDK9 component of P-TEFb and other Tat-activated kinases hyperphosphorylate the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B. In this purpose, it activates EIF2AK2/PKR which, in turns, may phosphorylate and target to degradation the inhibitor IkappaB-alpha which normally retains NF-kappa-B in the cytoplasm of unstimulated cells. Through its interaction with TBP, Tat may be involved in transcription initiation as well. Interacts with the cellular capping enzyme RNGTT to mediate co-transcriptional capping of viral mRNAs. Tat protein exerts as well a positive feedback on the translation of its cognate mRNA. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter. In the cytoplasm, Tat is thought to act as a translational activator of HIV-1 mRNAs (By similarity). Extracellular circulating Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as CD26, CXCR4, heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Endosomal low pH allows Tat to cross the endosome membrane to enter the cytosol and eventually further translocate into the nucleus, thereby inducing severe cell dysfunctions ranging from cell activation to cell death. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Tat seems to inhibit the HAT activity of KAT5/Tip60 and TAF1, and consequently modify the expression of specific cellular genes. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines (such as IL10) or cytokine receptors. May be involved in the derepression of host interleukin IL2 expression. Mediates the activation of cyclin-dependent kinases and dysregulation of microtubule network. Tat plays a role in T-cell and neurons apoptosis. Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Host extracellular matrix metalloproteinase MMP1 cleaves Tat and decreases Tat's mediated neurotoxicity. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. Binds to KDR/VEGFR-2. All these Tat-mediated effects enhance angiogenesis in Kaposi's sarcoma lesions (By similarity).		[[https://www.uniprot.org/uniprot/DPP4_HUMAN DPP4_HUMAN]] Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion. In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation. When overexpressed, enhanced cell proliferation, a process inhibited by GPC3. Acts also as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline.<ref>PMID:10951221</ref> <ref>PMID:17549790</ref> <ref>PMID:10570924</ref> <ref>PMID:10900005</ref> <ref>PMID:11772392</ref> <ref>PMID:14691230</ref> <ref>PMID:16651416</ref> <ref>PMID:17287217</ref> <ref>PMID:18708048</ref> [[https://www.uniprot.org/uniprot/TAT_HV1Z2 TAT_HV1Z2]] Nuclear transcriptional activator of viral gene expression, that is essential for viral transcription from the LTR promoter and replication. Acts as a sequence-specific molecular adapter, directing components of the cellular transcription machinery to the viral RNA to promote processive transcription elongation by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. In the absence of Tat, the RNA Pol II generates short or non-processive transcripts that terminate at approximately 60 bp from the initiation site. Tat associates with the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. This binding increases Tat's affinity for a hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA) and allows Tat/P-TEFb complex to bind cooperatively to TAR RNA. The CDK9 component of P-TEFb and other Tat-activated kinases hyperphosphorylate the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B. In this purpose, it activates EIF2AK2/PKR which, in turns, may phosphorylate and target to degradation the inhibitor IkappaB-alpha which normally retains NF-kappa-B in the cytoplasm of unstimulated cells. Through its interaction with TBP, Tat may be involved in transcription initiation as well. Interacts with the cellular capping enzyme RNGTT to mediate co-transcriptional capping of viral mRNAs. Tat protein exerts as well a positive feedback on the translation of its cognate mRNA. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter. In the cytoplasm, Tat is thought to act as a translational activator of HIV-1 mRNAs (By similarity). Extracellular circulating Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as CD26, CXCR4, heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Endosomal low pH allows Tat to cross the endosome membrane to enter the cytosol and eventually further translocate into the nucleus, thereby inducing severe cell dysfunctions ranging from cell activation to cell death. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Tat seems to inhibit the HAT activity of KAT5/Tip60 and TAF1, and consequently modify the expression of specific cellular genes. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines (such as IL10) or cytokine receptors. May be involved in the derepression of host interleukin IL2 expression. Mediates the activation of cyclin-dependent kinases and dysregulation of microtubule network. Tat plays a role in T-cell and neurons apoptosis. Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Host extracellular matrix metalloproteinase MMP1 cleaves Tat and decreases Tat's mediated neurotoxicity. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. Binds to KDR/VEGFR-2. All these Tat-mediated effects enhance angiogenesis in Kaposi's sarcoma lesions (By similarity).
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]

OCA at 08:11, 19 February 2020

2020-02-19T08:11:28Z

← Older revision		Revision as of 08:11, 19 February 2020
Line 1:		Line 1:

	==Crystal structure of HIV-1 Tat derived nonapeptides Tat(1-9) bound to the active site of Dipeptidyl peptidase IV (CD26)==		==Crystal structure of HIV-1 Tat derived nonapeptides Tat(1-9) bound to the active site of Dipeptidyl peptidase IV (CD26)==
	<StructureSection load='2bgr' size='340' side='right' caption='[[2bgr]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='2bgr' size='340' side='right'caption='[[2bgr]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2bgr]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BGR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BGR FirstGlance]. <br>		<table><tr><td colspan='2'>[[2bgr]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BGR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BGR FirstGlance]. <br>
Line 32:		Line 32:

	==See Also==		==See Also==
	*[[Dipeptidyl peptidase\|Dipeptidyl peptidase]]		*[[Dipeptidyl peptidase 3D structures\|Dipeptidyl peptidase 3D structures]]
	*[[Tat protein\|Tat protein]]		*[[Tat protein\|Tat protein]]
	== References ==		== References ==
Line 40:		Line 40:
	[[Category: Dipeptidyl-peptidase IV]]		[[Category: Dipeptidyl-peptidase IV]]
	[[Category: Human]]		[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Fan, H]]		[[Category: Fan, H]]
	[[Category: Liu, J]]		[[Category: Liu, J]]

OCA at 06:39, 16 May 2018

2018-05-16T06:39:19Z

← Older revision		Revision as of 06:39, 16 May 2018
Line 1:		Line 1:
	==~~CRYSTAL STRUCTURE OF~~ HIV-1 ~~TAT DERIVED NONAPEPTIDES TAT~~(1-9) ~~BOUND TO THE ACTIVE SITE OF DIPEPTIDYL PEPTIDASE~~ IV (CD26)==
			==Crystal structure of HIV-1 Tat derived nonapeptides Tat(1-9) bound to the active site of Dipeptidyl peptidase IV (CD26)==
	<StructureSection load='2bgr' size='340' side='right' caption='[[2bgr]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='2bgr' size='340' side='right' caption='[[2bgr]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2bgr]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BGR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BGR FirstGlance]. <br>		<table><tr><td colspan='2'>[[2bgr]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BGR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BGR FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=~~NAG~~:N-~~ACETYL~~-~~D-GLUCOSAMINE~~'>~~NAG~~</scene>, <scene name='pdbligand=~~FUC~~:~~ALPHA~~-L-~~FUCOSE~~'>~~FUC~~</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1j2e\|1j2e]], [[1n1m\|1n1m]], [[1nu6\|1nu6]], [[1nu8\|1nu8]], [[1pfq\|1pfq]], [[1r9m\|1r9m]], [[1rwq\|1rwq]], [[1tk3\|1tk3]], [[1tkr\|1tkr]], [[1u8e\|1u8e]], [[1w1i\|1w1i]], [[2bgn\|2bgn]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1j2e\|1j2e]], [[1n1m\|1n1m]], [[1nu6\|1nu6]], [[1nu8\|1nu8]], [[1pfq\|1pfq]], [[1r9m\|1r9m]], [[1rwq\|1rwq]], [[1tk3\|1tk3]], [[1tkr\|1tkr]], [[1u8e\|1u8e]], [[1w1i\|1w1i]], [[2bgn\|2bgn]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dipeptidyl-peptidase_IV Dipeptidyl-peptidase IV], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.5 3.4.14.5] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dipeptidyl-peptidase_IV Dipeptidyl-peptidase IV], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.5 3.4.14.5] </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=2bgr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bgr OCA], [http://pdbe.org/2bgr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2bgr RCSB], [http://www.ebi.ac.uk/pdbsum/2bgr 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=2bgr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bgr OCA], [http://pdbe.org/2bgr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2bgr RCSB], [http://www.ebi.ac.uk/pdbsum/2bgr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2bgr ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 14:		Line 15:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bg/2bgr_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bg/2bgr_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=2bgr ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 01:43, 12 September 2015

2015-09-12T01:43:16Z

← Older revision		Revision as of 01:43, 12 September 2015
Line 2:		Line 2:
	<StructureSection load='2bgr' size='340' side='right' caption='[[2bgr]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='2bgr' size='340' side='right' caption='[[2bgr]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2bgr]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BGR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BGR FirstGlance]. <br>		<table><tr><td colspan='2'>[[2bgr]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BGR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BGR FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1j2e\|1j2e]], [[1n1m\|1n1m]], [[1nu6\|1nu6]], [[1nu8\|1nu8]], [[1pfq\|1pfq]], [[1r9m\|1r9m]], [[1rwq\|1rwq]], [[1tk3\|1tk3]], [[1tkr\|1tkr]], [[1u8e\|1u8e]], [[1w1i\|1w1i]], [[2bgn\|2bgn]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1j2e\|1j2e]], [[1n1m\|1n1m]], [[1nu6\|1nu6]], [[1nu8\|1nu8]], [[1pfq\|1pfq]], [[1r9m\|1r9m]], [[1rwq\|1rwq]], [[1tk3\|1tk3]], [[1tkr\|1tkr]], [[1u8e\|1u8e]], [[1w1i\|1w1i]], [[2bgn\|2bgn]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dipeptidyl-peptidase_IV Dipeptidyl-peptidase IV], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.5 3.4.14.5] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dipeptidyl-peptidase_IV Dipeptidyl-peptidase IV], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.5 3.4.14.5] </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=2bgr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bgr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2bgr RCSB], [http://www.ebi.ac.uk/pdbsum/2bgr 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=2bgr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bgr OCA], [http://pdbe.org/2bgr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2bgr RCSB], [http://www.ebi.ac.uk/pdbsum/2bgr PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 28:		Line 28:
	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 2bgr" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 37:		Line 38:
	</StructureSection>		</StructureSection>
	[[Category: Dipeptidyl-peptidase IV]]		[[Category: Dipeptidyl-peptidase IV]]
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Fan, H]]		[[Category: Fan, H]]
	[[Category: Liu, J]]		[[Category: Liu, J]]

OCA at 22:10, 25 December 2014

2014-12-25T22:10:21Z

← Older revision		Revision as of 22:10, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2bgr]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BGR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BGR FirstGlance]. <br>		<table><tr><td colspan='2'>[[2bgr]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BGR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BGR FirstGlance]. <br>
	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene><br>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene></td></tr>
	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1j2e\|1j2e]], [[1n1m\|1n1m]], [[1nu6\|1nu6]], [[1nu8\|1nu8]], [[1pfq\|1pfq]], [[1r9m\|1r9m]], [[1rwq\|1rwq]], [[1tk3\|1tk3]], [[1tkr\|1tkr]], [[1u8e\|1u8e]], [[1w1i\|1w1i]], [[2bgn\|2bgn]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1j2e\|1j2e]], [[1n1m\|1n1m]], [[1nu6\|1nu6]], [[1nu8\|1nu8]], [[1pfq\|1pfq]], [[1r9m\|1r9m]], [[1rwq\|1rwq]], [[1tk3\|1tk3]], [[1tkr\|1tkr]], [[1u8e\|1u8e]], [[1w1i\|1w1i]], [[2bgn\|2bgn]]</td></tr>
	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dipeptidyl-peptidase_IV Dipeptidyl-peptidase IV], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.5 3.4.14.5] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dipeptidyl-peptidase_IV Dipeptidyl-peptidase IV], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.5 3.4.14.5] </span></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=2bgr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bgr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2bgr RCSB], [http://www.ebi.ac.uk/pdbsum/2bgr 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=2bgr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bgr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2bgr RCSB], [http://www.ebi.ac.uk/pdbsum/2bgr PDBsum]</span></td></tr>
	<table>		</table>
			== Function ==
			[[http://www.uniprot.org/uniprot/DPP4_HUMAN DPP4_HUMAN]] Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion. In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation. When overexpressed, enhanced cell proliferation, a process inhibited by GPC3. Acts also as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline.<ref>PMID:10951221</ref> <ref>PMID:17549790</ref> <ref>PMID:10570924</ref> <ref>PMID:10900005</ref> <ref>PMID:11772392</ref> <ref>PMID:14691230</ref> <ref>PMID:16651416</ref> <ref>PMID:17287217</ref> <ref>PMID:18708048</ref> [[http://www.uniprot.org/uniprot/TAT_HV1Z2 TAT_HV1Z2]] Nuclear transcriptional activator of viral gene expression, that is essential for viral transcription from the LTR promoter and replication. Acts as a sequence-specific molecular adapter, directing components of the cellular transcription machinery to the viral RNA to promote processive transcription elongation by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. In the absence of Tat, the RNA Pol II generates short or non-processive transcripts that terminate at approximately 60 bp from the initiation site. Tat associates with the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. This binding increases Tat's affinity for a hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA) and allows Tat/P-TEFb complex to bind cooperatively to TAR RNA. The CDK9 component of P-TEFb and other Tat-activated kinases hyperphosphorylate the C-terminus of RNA Pol II that becomes stabilized and much more processive. Other factors such as HTATSF1/Tat-SF1, SUPT5H/SPT5, and HTATIP2 are also important for Tat's function. Besides its effect on RNA Pol II processivity, Tat induces chromatin remodeling of proviral genes by recruiting the histone acetyltransferases (HATs) CREBBP, EP300 and PCAF to the chromatin. This also contributes to the increase in proviral transcription rate, especially when the provirus integrates in transcriptionally silent region of the host genome. To ensure maximal activation of the LTR, Tat mediates nuclear translocation of NF-kappa-B. In this purpose, it activates EIF2AK2/PKR which, in turns, may phosphorylate and target to degradation the inhibitor IkappaB-alpha which normally retains NF-kappa-B in the cytoplasm of unstimulated cells. Through its interaction with TBP, Tat may be involved in transcription initiation as well. Interacts with the cellular capping enzyme RNGTT to mediate co-transcriptional capping of viral mRNAs. Tat protein exerts as well a positive feedback on the translation of its cognate mRNA. Tat can reactivate a latently infected cell by penetrating in it and transactivating its LTR promoter. In the cytoplasm, Tat is thought to act as a translational activator of HIV-1 mRNAs (By similarity). Extracellular circulating Tat can be endocytosed by surrounding uninfected cells via the binding to several surface receptors such as CD26, CXCR4, heparan sulfate proteoglycans (HSPG) or LDLR. Neurons are rarely infected, but they internalize Tat via their LDLR. Endosomal low pH allows Tat to cross the endosome membrane to enter the cytosol and eventually further translocate into the nucleus, thereby inducing severe cell dysfunctions ranging from cell activation to cell death. Through its interaction with nuclear HATs, Tat is potentially able to control the acetylation-dependent cellular gene expression. Tat seems to inhibit the HAT activity of KAT5/Tip60 and TAF1, and consequently modify the expression of specific cellular genes. Modulates the expression of many cellular genes involved in cell survival, proliferation or in coding for cytokines (such as IL10) or cytokine receptors. May be involved in the derepression of host interleukin IL2 expression. Mediates the activation of cyclin-dependent kinases and dysregulation of microtubule network. Tat plays a role in T-cell and neurons apoptosis. Tat induced neurotoxicity and apoptosis probably contribute to neuroAIDS. Host extracellular matrix metalloproteinase MMP1 cleaves Tat and decreases Tat's mediated neurotoxicity. Circulating Tat also acts as a chemokine-like and/or growth factor-like molecule that binds to specific receptors on the surface of the cells, affecting many cellular pathways. In the vascular system, Tat binds to ITGAV/ITGB3 and ITGA5/ITGB1 integrins dimers at the surface of endothelial cells and competes with bFGF for heparin-binding sites, leading to an excess of soluble bFGF. Binds to KDR/VEGFR-2. All these Tat-mediated effects enhance angiogenesis in Kaposi's sarcoma lesions (By similarity).
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 36:		Line 38:
	[[Category: Dipeptidyl-peptidase IV]]		[[Category: Dipeptidyl-peptidase IV]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Fan, H.]]		[[Category: Fan, H]]
	[[Category: Liu, J.]]		[[Category: Liu, J]]
	[[Category: Reutter, W.]]		[[Category: Reutter, W]]
	[[Category: Saenger, W.]]		[[Category: Saenger, W]]
	[[Category: Weihofen, W A.]]		[[Category: Weihofen, W A]]
	[[Category: Alpha/beta-hydrolase fold]]		[[Category: Alpha/beta-hydrolase fold]]
	[[Category: Beta-propeller fold]]		[[Category: Beta-propeller fold]]

OCA at 05:48, 29 September 2014

2014-09-29T05:48:37Z

← Older revision		Revision as of 05:48, 29 September 2014
Line 1:		Line 1:
	[[Image:~~2bgr~~.~~png~~\|~~left~~\|~~200px~~]]		==CRYSTAL STRUCTURE OF HIV-1 TAT DERIVED NONAPEPTIDES TAT(1-9) BOUND TO THE ACTIVE SITE OF DIPEPTIDYL PEPTIDASE IV (CD26)==
			<StructureSection load='2bgr' size='340' side='right' caption='[[2bgr]], [[Resolution\|resolution]] 2.00Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[2bgr]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BGR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BGR FirstGlance]. <br>
			</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene><br>
			<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1j2e\|1j2e]], [[1n1m\|1n1m]], [[1nu6\|1nu6]], [[1nu8\|1nu8]], [[1pfq\|1pfq]], [[1r9m\|1r9m]], [[1rwq\|1rwq]], [[1tk3\|1tk3]], [[1tkr\|1tkr]], [[1u8e\|1u8e]], [[1w1i\|1w1i]], [[2bgn\|2bgn]]</td></tr>
			<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dipeptidyl-peptidase_IV Dipeptidyl-peptidase IV], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.5 3.4.14.5] </span></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=2bgr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bgr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2bgr RCSB], [http://www.ebi.ac.uk/pdbsum/2bgr 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/bg/2bgr_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 ==
			CD26 or dipeptidyl-peptidase IV (DPPIV) is engaged in immune functions by co-stimulatory effects on activation and proliferation of T lymphocytes, binding to adenosine deaminase, and regulation of various chemokines and cytokines. DPPIV peptidase activity is inhibited by both Tat protein from human immunodeficiency virus (HIV)-1 and its N-terminal nonapeptide Tat-(1-9) with amino acid sequence MDPVDPNIE, suggesting that DPPIV mediates immunosuppressive effects of Tat protein. The 2.0- and 3.15-A resolution crystal structures of the binary complex between human DPPIV and nonapeptide Tat-(1-9) and the ternary complex between the variant MWPVDPNIE, called Trp(2)-Tat-(1-9), and DPPIV bound to adenosine deaminase show that Tat-(1-9) and Trp(2)-Tat-(1-9) are located in the active site of DPPIV. The interaction pattern of DPPIV with Trp(2)-Tat-(1-9) is tighter than that with Tat-(1-9), in agreement with inhibition constants (K(i)) of 2 x 10(-6) and 250 x 10(-6) m, respectively. Both peptides cannot be cleaved by DPPIV because the binding pockets of the N-terminal 2 residues are interchanged compared with natural substrates: the N-terminal methionine occupies the hydrophobic S1 pocket of DPPIV that normally accounts for substrate specificity by binding the penultimate residue. Because the N-terminal sequence of the thromboxane A2 receptor resembles the Trp(2)-Tat-(1-9) peptide, a possible interaction with DPPIV is postulated.

	~~{{STRUCTURE_2bgr\| PDB=2bgr \| SCENE= }}~~		Crystal structures of HIV-1 Tat-derived nonapeptides Tat-(1-9) and Trp2-Tat-(1-9) bound to the active site of dipeptidyl-peptidase IV (CD26).,Weihofen WA, Liu J, Reutter W, Saenger W, Fan H J Biol Chem. 2005 Apr 15;280(15):14911-7. Epub 2005 Jan 28. PMID:15695814<ref>PMID:15695814</ref>

	~~===CRYSTAL STRUCTURE OF HIV-1 TAT DERIVED NONAPEPTIDES TAT(1-9) BOUND TO THE ACTIVE SITE OF DIPEPTIDYL PEPTIDASE IV (CD26)===~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
	~~{{ABSTRACT_PUBMED_15695814}}~~

	~~==About this Structure==~~
	~~[[2bgr]] is~~ a ~~4 chain structure with sequence from [http://en.wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full crystallographic information is available from [http://oca~~.~~weizmann.ac.il/oca-bin~~/~~ocashort?id=2BGR OCA].~~

	==See Also==		==See Also==
	*[[Dipeptidyl peptidase\|Dipeptidyl peptidase]]		*[[Dipeptidyl peptidase\|Dipeptidyl peptidase]]
	*[[Tat protein\|Tat protein]]		*[[Tat protein\|Tat protein]]
			== References ==
	==~~Reference~~==		<references/>
	<~~ref group="xtra">PMID:015695814<~~/~~ref~~><~~references group="xtra"~~/>		__TOC__
			</StructureSection>
	[[Category: Dipeptidyl-peptidase IV]]		[[Category: Dipeptidyl-peptidase IV]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]

OCA at 22:13, 20 October 2012

2012-10-20T22:13:59Z

← Older revision		Revision as of 22:13, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
	[[2bgr]] is a 4 chain structure ~~of [[Dipeptidyl peptidase]] and [[Tat protein]]~~ with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BGR OCA].		[[2bgr]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BGR OCA].

	==See Also==		==See Also==

OCA at 15:38, 27 July 2012

2012-07-27T15:38:27Z

← Older revision		Revision as of 15:38, 27 July 2012
Line 1:		Line 1:
	[[Image:2bgr.png\|left\|200px]]		[[Image:2bgr.png\|left\|200px]]

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_2bgr", 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_2bgr\| PDB=2bgr \| SCENE= }}		{{STRUCTURE_2bgr\| PDB=2bgr \| SCENE= }}

	===CRYSTAL STRUCTURE OF HIV-1 TAT DERIVED NONAPEPTIDES TAT(1-9) BOUND TO THE ACTIVE SITE OF DIPEPTIDYL PEPTIDASE IV (CD26)===		===CRYSTAL STRUCTURE OF HIV-1 TAT DERIVED NONAPEPTIDES TAT(1-9) BOUND TO THE ACTIVE SITE OF DIPEPTIDYL PEPTIDASE IV (CD26)===


	~~<!--~~
	~~The line below this paragraph, {{ABSTRACT_PUBMED_15695814}}, adds the Publication Abstract to the page~~
	~~(as it appears on PubMed at http://www.pubmed.gov), where 15695814 is the PubMed ID number.~~
	~~-->~~
	{{ABSTRACT_PUBMED_15695814}}		{{ABSTRACT_PUBMED_15695814}}

	==About this Structure==		==About this Structure==
	[[2bgr]] is a 4 chain structure of [[Dipeptidyl peptidase]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BGR OCA].		[[2bgr]] is a 4 chain structure of [[Dipeptidyl peptidase]] and [[Tat protein]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BGR OCA].

	==See Also==		==See Also==
	*[[Dipeptidyl peptidase]]		*[[Dipeptidyl peptidase\|Dipeptidyl peptidase]]
			*[[Tat protein\|Tat protein]]

	==Reference==		==Reference==

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

2011-08-24T06:11:47Z

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

← Older revision	Revision as of 06:11, 24 August 2011
(No difference)