6cri
From Proteopedia
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<SX load='6cri' size='340' side='right' viewer='molstar' caption='[[6cri]], [[Resolution|resolution]] 6.80Å' scene=''> | <SX load='6cri' size='340' side='right' viewer='molstar' caption='[[6cri]], [[Resolution|resolution]] 6.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6cri]] is a 24 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[6cri]] is a 24 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CRI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CRI FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 6.8Å</td></tr> |
| - | <tr id=' | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6cri FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cri OCA], [https://pdbe.org/6cri PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cri RCSB], [https://www.ebi.ac.uk/pdbsum/6cri PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cri ProSAT]</span></td></tr> |
</table> | </table> | ||
| - | == Disease == | ||
| - | [[http://www.uniprot.org/uniprot/AP1S3_HUMAN AP1S3_HUMAN]] Acrodermatitis continua suppurativa of Hallopeau;Generalized pustular psoriasis;Pustulosis palmaris et plantaris. Disease susceptibility is associated with variations affecting the gene represented in this entry. | ||
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/NEF_HV1B1 NEF_HV1B1] 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). 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). 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). 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). Extracellular Nef protein targets CD4(+) T-lymphocytes for apoptosis by interacting with CXCR4 surface receptors (By similarity).[https://www.uniprot.org/uniprot/BST2_HUMAN BST2_HUMAN] IFN-induced antiviral host restriction factor which efficiently blocks the release of diverse mammalian enveloped viruses by directly tethering nascent virions to the membranes of infected cells. Acts as a direct physical tether, holding virions to the cell membrane and linking virions to each other. The tethered virions can be internalized by endocytosis and subsequently degraded or they can remain on the cell surface. In either case, their spread as cell-free virions is restricted. Its target viruses belong to diverse families, including retroviridae: human immunodeficiency virus type 1 (HIV-1), human immunodeficiency virus type 2 (HIV-2), simian immunodeficiency viruses (SIVs), equine infectious anemia virus (EIAV), feline immunodeficiency virus (FIV), prototype foamy virus (PFV), Mason-Pfizer monkey virus (MPMV), human T-cell leukemia virus type 1 (HTLV-1), Rous sarcoma virus (RSV) and murine leukemia virus (MLV), flavivirideae: hepatitis C virus (HCV), filoviridae: ebola virus (EBOV) and marburg virus (MARV), arenaviridae: lassa virus (LASV) and machupo virus (MACV), herpesviridae: kaposis sarcoma-associated herpesvirus (KSHV), rhabdoviridae: vesicular stomatitis virus (VSV), orthomyxoviridae: influenza A virus, and paramyxoviridae: nipah virus. Can inhibit cell surface proteolytic activity of MMP14 causing decreased activation of MMP15 which results in inhibition of cell growth and migration. Can stimulate signaling by LILRA4/ILT7 and consequently provide negative feedback to the production of IFN by plasmacytoid dendritic cells in response to viral infection. Plays a role in the organization of the subapical actin cytoskeleton in polarized epithelial cells.<ref>PMID:18342597</ref> <ref>PMID:18200009</ref> <ref>PMID:19879838</ref> <ref>PMID:19564354</ref> <ref>PMID:19036818</ref> <ref>PMID:19179289</ref> <ref>PMID:20686043</ref> <ref>PMID:20943977</ref> <ref>PMID:20419159</ref> <ref>PMID:21529378</ref> <ref>PMID:21621240</ref> <ref>PMID:22065321</ref> <ref>PMID:22520941</ref> <ref>PMID:20399176</ref> <ref>PMID:20940320</ref> |
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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==See Also== | ==See Also== | ||
*[[Adaptin 3D structures|Adaptin 3D structures]] | *[[Adaptin 3D structures|Adaptin 3D structures]] | ||
| + | *[[Protein Nef 3D structures|Protein Nef 3D structures]] | ||
| + | *[[Tetherin|Tetherin]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</SX> | </SX> | ||
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| + | [[Category: Human immunodeficiency virus 1]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Mus musculus]] |
| - | [[Category: Buffalo | + | [[Category: Buffalo CZ]] |
| - | [[Category: Hurley | + | [[Category: Hurley JH]] |
| - | [[Category: Morris | + | [[Category: Morris KL]] |
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Current revision
Structure of the cargo bound AP-1:Arf1:tetherin-Nef stable closed trimer
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