We apologize for Proteopedia being slow to respond. For the past two years, a new implementation of Proteopedia has been being built. Soon, it will replace this 18-year old system. All existing content will be moved to the new system at a date that will be announced here.

4u5w

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (07:25, 27 September 2023) (edit) (undo)
 
(6 intermediate revisions not shown.)
Line 1: Line 1:
 +
==Crystal Structure of HIV-1 Nef-SF2 Core Domain in Complex with the Src Family Kinase Hck SH3-SH2 Tandem Regulatory Domains==
==Crystal Structure of HIV-1 Nef-SF2 Core Domain in Complex with the Src Family Kinase Hck SH3-SH2 Tandem Regulatory Domains==
-
<StructureSection load='4u5w' size='340' side='right' caption='[[4u5w]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
+
<StructureSection load='4u5w' size='340' side='right'caption='[[4u5w]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[4u5w]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U5W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U5W FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[4u5w]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/HIV-1_M:B_ARV2/SF2 HIV-1 M:B_ARV2/SF2] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U5W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4U5W FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</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]] 1.86&#8491;</td></tr>
-
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene></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=4u5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u5w OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4u5w RCSB], [http://www.ebi.ac.uk/pdbsum/4u5w PDBsum]</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=4u5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u5w OCA], [https://pdbe.org/4u5w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4u5w RCSB], [https://www.ebi.ac.uk/pdbsum/4u5w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4u5w ProSAT]</span></td></tr>
</table>
</table>
-
== Disease ==
 
-
[[http://www.uniprot.org/uniprot/HCK_HUMAN HCK_HUMAN]] Note=Aberrant activation of HCK by HIV-1 protein Nef enhances HIV-1 replication and contributes to HIV-1 pathogenicity.<ref>PMID:19114024</ref> <ref>PMID:20452982</ref> Note=Aberrant activation of HCK, e.g. by the BCR-ABL fusion protein, promotes cancer cell proliferation.<ref>PMID:19114024</ref> <ref>PMID:20452982</ref>
 
== Function ==
== Function ==
-
[[http://www.uniprot.org/uniprot/NEF_HV1A2 NEF_HV1A2]] Factor of infectivity and pathogenicity, required for optimal virus replication. Alters numerous pathways of T-lymphocytes function and down-regulates immunity surface molecules in order to evade host defense and increase viral infectivity. Alters the functionality of other immunity cells, like dendritic cells, monocytes/macrophages and NK cells. One of the earliest and most abundantly expressed viral proteins (By similarity).<ref>PMID:9218412</ref> <ref>PMID:10224289</ref> <ref>PMID:10208934</ref> <ref>PMID:11070003</ref> <ref>PMID:11420046</ref> <ref>PMID:11689886</ref> In infected CD4(+) T-lymphocytes, down-regulates the surface MHC-I, mature MHC-II, CD4, CD28, CCR5 and CXCR4 molecules. Mediates internalization and degradation of host CD4 through the interaction of with the cytoplasmic tail of CD4, the recruitment of AP-2 (clathrin adapter protein complex 2), internalization through clathrin coated pits, and subsequent transport to endosomes and lysosomes for degradation. Diverts host MHC-I molecules to the trans-Golgi network-associated endosomal compartments by an endocytic pathway to finally target them for degradation. MHC-I down-regulation may involve AP-1 (clathrin adapter protein complex 1) or possibly Src family kinase-ZAP70/Syk-PI3K cascade recruited by PACS2. In consequence infected cells are masked for immune recognition by cytotoxic T-lymphocytes. Decreasing the number of immune receptors also prevents reinfection by more HIV particles (superinfection) (By similarity).<ref>PMID:9218412</ref> <ref>PMID:10224289</ref> <ref>PMID:10208934</ref> <ref>PMID:11070003</ref> <ref>PMID:11420046</ref> <ref>PMID:11689886</ref> Bypasses host T-cell signaling by inducing a transcriptional program nearly identical to that of anti-CD3 cell activation. Interaction with TCR-zeta chain up-regulates the Fas ligand (FasL). Increasing surface FasL molecules and decreasing surface MHC-I molecules on infected CD4(+) cells send attacking cytotoxic CD8+ T-lymphocytes into apoptosis (By similarity).<ref>PMID:9218412</ref> <ref>PMID:10224289</ref> <ref>PMID:10208934</ref> <ref>PMID:11070003</ref> <ref>PMID:11420046</ref> <ref>PMID:11689886</ref> Plays a role in optimizing the host cell environment for viral replication without causing cell death by apoptosis. Protects the infected cells from apoptosis in order to keep them alive until the next virus generation is ready to strike. Inhibits the Fas and TNFR-mediated death signals by blocking MAP3K5. Interacts and decreases the half-life of p53, protecting the infected cell against p53-mediated apoptosis. Inhibits the apoptotic signals regulated by the Bcl-2 family proteins through the formation of a Nef/PI3-kinase/PAK2 complex that leads to activation of PAK2 and induces phosphorylation of Bad (By similarity).<ref>PMID:9218412</ref> <ref>PMID:10224289</ref> <ref>PMID:10208934</ref> <ref>PMID:11070003</ref> <ref>PMID:11420046</ref> <ref>PMID:11689886</ref> Extracellular Nef protein targets CD4(+) T-lymphocytes for apoptosis by interacting with CXCR4 surface receptors (By similarity).<ref>PMID:9218412</ref> <ref>PMID:10224289</ref> <ref>PMID:10208934</ref> <ref>PMID:11070003</ref> <ref>PMID:11420046</ref> <ref>PMID:11689886</ref> [[http://www.uniprot.org/uniprot/HCK_HUMAN HCK_HUMAN]] Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS.<ref>PMID:8132624</ref> <ref>PMID:7535819</ref> <ref>PMID:9406996</ref> <ref>PMID:9407116</ref> <ref>PMID:10092522</ref> <ref>PMID:10779760</ref> <ref>PMID:10973280</ref> <ref>PMID:12411494</ref> <ref>PMID:11741929</ref> <ref>PMID:11904303</ref> <ref>PMID:11896602</ref> <ref>PMID:15010462</ref> <ref>PMID:15952790</ref> <ref>PMID:15998323</ref> <ref>PMID:17535448</ref> <ref>PMID:17310994</ref> <ref>PMID:19114024</ref> <ref>PMID:19903482</ref> <ref>PMID:20452982</ref>
+
[https://www.uniprot.org/uniprot/NEF_HV1A2 NEF_HV1A2] Factor of infectivity and pathogenicity, required for optimal virus replication. Alters numerous pathways of T-lymphocytes function and down-regulates immunity surface molecules in order to evade host defense and increase viral infectivity. Alters the functionality of other immunity cells, like dendritic cells, monocytes/macrophages and NK cells. One of the earliest and most abundantly expressed viral proteins (By similarity).<ref>PMID:9218412</ref> <ref>PMID:10224289</ref> <ref>PMID:10208934</ref> <ref>PMID:11070003</ref> <ref>PMID:11420046</ref> <ref>PMID:11689886</ref> In infected CD4(+) T-lymphocytes, down-regulates the surface MHC-I, mature MHC-II, CD4, CD28, CCR5 and CXCR4 molecules. Mediates internalization and degradation of host CD4 through the interaction of with the cytoplasmic tail of CD4, the recruitment of AP-2 (clathrin adapter protein complex 2), internalization through clathrin coated pits, and subsequent transport to endosomes and lysosomes for degradation. Diverts host MHC-I molecules to the trans-Golgi network-associated endosomal compartments by an endocytic pathway to finally target them for degradation. MHC-I down-regulation may involve AP-1 (clathrin adapter protein complex 1) or possibly Src family kinase-ZAP70/Syk-PI3K cascade recruited by PACS2. In consequence infected cells are masked for immune recognition by cytotoxic T-lymphocytes. Decreasing the number of immune receptors also prevents reinfection by more HIV particles (superinfection) (By similarity).<ref>PMID:9218412</ref> <ref>PMID:10224289</ref> <ref>PMID:10208934</ref> <ref>PMID:11070003</ref> <ref>PMID:11420046</ref> <ref>PMID:11689886</ref> Bypasses host T-cell signaling by inducing a transcriptional program nearly identical to that of anti-CD3 cell activation. Interaction with TCR-zeta chain up-regulates the Fas ligand (FasL). Increasing surface FasL molecules and decreasing surface MHC-I molecules on infected CD4(+) cells send attacking cytotoxic CD8+ T-lymphocytes into apoptosis (By similarity).<ref>PMID:9218412</ref> <ref>PMID:10224289</ref> <ref>PMID:10208934</ref> <ref>PMID:11070003</ref> <ref>PMID:11420046</ref> <ref>PMID:11689886</ref> Plays a role in optimizing the host cell environment for viral replication without causing cell death by apoptosis. Protects the infected cells from apoptosis in order to keep them alive until the next virus generation is ready to strike. Inhibits the Fas and TNFR-mediated death signals by blocking MAP3K5. Interacts and decreases the half-life of p53, protecting the infected cell against p53-mediated apoptosis. Inhibits the apoptotic signals regulated by the Bcl-2 family proteins through the formation of a Nef/PI3-kinase/PAK2 complex that leads to activation of PAK2 and induces phosphorylation of Bad (By similarity).<ref>PMID:9218412</ref> <ref>PMID:10224289</ref> <ref>PMID:10208934</ref> <ref>PMID:11070003</ref> <ref>PMID:11420046</ref> <ref>PMID:11689886</ref> Extracellular Nef protein targets CD4(+) T-lymphocytes for apoptosis by interacting with CXCR4 surface receptors (By similarity).<ref>PMID:9218412</ref> <ref>PMID:10224289</ref> <ref>PMID:10208934</ref> <ref>PMID:11070003</ref> <ref>PMID:11420046</ref> <ref>PMID:11689886</ref>
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
Line 19: Line 18:
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
</div>
 +
<div class="pdbe-citations 4u5w" style="background-color:#fffaf0;"></div>
 +
 +
==See Also==
 +
*[[Protein Nef 3D structures|Protein Nef 3D structures]]
 +
*[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
-
[[Category: Non-specific protein-tyrosine kinase]]
+
[[Category: HIV-1 M:B_ARV2/SF2]]
-
[[Category: Alvarado, J J.]]
+
[[Category: Homo sapiens]]
-
[[Category: Smithgall, T E.]]
+
[[Category: Large Structures]]
-
[[Category: Yeh, J I.]]
+
[[Category: Alvarado JJ]]
-
[[Category: Hck]]
+
[[Category: Smithgall TE]]
-
[[Category: Hiv-1]]
+
[[Category: Yeh JI]]
-
[[Category: Nef]]
+
-
[[Category: Nef-hck complex]]
+
-
[[Category: Protein-protein complex]]
+
-
[[Category: Sfk]]
+
-
[[Category: Sh2]]
+
-
[[Category: Sh3]]
+
-
[[Category: Sh3-sh2 regulatory domain]]
+
-
[[Category: Src family kinase]]
+
-
[[Category: Viral protein-transferase complex]]
+
-
[[Category: Virus]]
+

Current revision

Crystal Structure of HIV-1 Nef-SF2 Core Domain in Complex with the Src Family Kinase Hck SH3-SH2 Tandem Regulatory Domains

PDB ID 4u5w

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4u5w"
Personal tools