View source for 3rea


==HIV-1 Nef protein in complex with engineered Hck-SH3 domain==
<StructureSection load='3rea' size='340' side='right'caption='[[3rea]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3rea]] 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=3REA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3REA FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</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=3rea FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rea OCA], [https://pdbe.org/3rea PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rea RCSB], [https://www.ebi.ac.uk/pdbsum/3rea PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rea ProSAT]</span></td></tr>
</table>
== Function ==
[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> 

==See Also==
*[[Protein Nef 3D structures|Protein Nef 3D structures]]
*[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: HIV-1 M:B_ARV2/SF2]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Blankenfeldt W]]
[[Category: Geyer M]]
[[Category: Schulte A]]