Proteopedia

6dff: Difference between revisions

← Older edit
No edit summary
No edit summary
 
(3 intermediate revisions by the same user not shown)
Line 1: Line 1:


==Structure of the cargo bound AP-1:Arf1:tetherin-Nef monomer==
==Structure of the cargo bound AP-1:Arf1:tetherin-Nef monomer==
<StructureSection load='6dff' size='340' side='right' caption='[[6dff]], [[Resolution|resolution]] 3.90&Aring;' scene=''>
<SX load='6dff' size='340' side='right' viewer='molstar' caption='[[6dff]], [[Resolution|resolution]] 3.90&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6dff]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DFF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DFF FirstGlance]. <br>
<table><tr><td colspan='2'>[[6dff]] is a 8 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=6DFF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DFF FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.9&#8491;</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=6dff FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dff OCA], [http://pdbe.org/6dff PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dff RCSB], [http://www.ebi.ac.uk/pdbsum/6dff PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dff ProSAT]</span></td></tr>
<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'>[https://proteopedia.org/fgij/fg.htm?mol=6dff FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dff OCA], [https://pdbe.org/6dff PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dff RCSB], [https://www.ebi.ac.uk/pdbsum/6dff PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dff 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 ==
[[http://www.uniprot.org/uniprot/AP1S3_HUMAN AP1S3_HUMAN]] Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules. Involved in TLR3 trafficking (PubMed:24791904).<ref>PMID:24791904</ref>  [[http://www.uniprot.org/uniprot/AP1G1_MOUSE AP1G1_MOUSE]] Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules. [[http://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> [[http://www.uniprot.org/uniprot/ARF1_HUMAN ARF1_HUMAN]] GTP-binding protein that functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase. Involved in protein trafficking among different compartments. Modulates vesicle budding and uncoating within the Golgi complex. Deactivation induces the redistribution of the entire Golgi complex to the endoplasmic reticulum, suggesting a crucial role in protein trafficking. In its GTP-bound form, its triggers the association with coat proteins with the Golgi membrane. The hydrolysis of ARF1-bound GTP, which is mediated by ARFGAPs proteins, is required for dissociation of coat proteins from Golgi membranes and vesicles. [[http://www.uniprot.org/uniprot/AP1B1_HUMAN AP1B1_HUMAN]] Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules. [[http://www.uniprot.org/uniprot/AP1M1_MOUSE AP1M1_MOUSE]] Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the trans-Golgi network (TGN) and endosomes. The AP complexes mediate the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules.
[https://www.uniprot.org/uniprot/Q90VU7_9HIV1 Q90VU7_9HIV1] [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;">
== Publication Abstract from PubMed ==
The HIV accessory protein Nef counteracts immune defenses by subverting coated vesicle pathways. The 3.7 A cryo-EM structure of a closed trimer of the clathrin adaptor AP-1, the small GTPase Arf1, HIV-1 Nef, and the cytosolic tail of the restriction factor tetherin suggested a mechanism for inactivating tetherin by Golgi retention. The 4.3 A structure of a mutant Nef-induced dimer of AP-1 showed how the closed trimer is regulated by the dileucine loop of Nef. HDX-MS and mutational analysis were used to show how cargo dynamics leads to alternative Arf1 trimerization, directing Nef targets to be either retained at the trans-Golgi or sorted to lysosomes. Phosphorylation of the NL4-3 M-Nef was shown to regulate AP-1 trimerization, explaining how O-Nefs lacking this phosphosite counteract tetherin but most M-Nefs do not. These observations show how the higher-order organization of a vesicular coat can be allosterically modulated to direct cargoes to distinct fates.


HIV-1 Nefs Are Cargo-Sensitive AP-1 Trimerization Switches in Tetherin Downregulation.,Morris KL, Buffalo CZ, Sturzel CM, Heusinger E, Kirchhoff F, Ren X, Hurley JH Cell. 2018 Jul 26;174(3):659-671.e14. doi: 10.1016/j.cell.2018.07.004. PMID:30053425<ref>PMID:30053425</ref>
==See Also==
 
*[[Adaptin 3D structures|Adaptin 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
*[[Tetherin|Tetherin]]
</div>
<div class="pdbe-citations 6dff" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</SX>
[[Category: Buffalo, C Z]]
[[Category: Homo sapiens]]
[[Category: Hurley, J H]]
[[Category: Human immunodeficiency virus 1]]
[[Category: Morris, K L]]
[[Category: Large Structures]]
[[Category: Ren, X]]
[[Category: Mus musculus]]
[[Category: Ap]]
[[Category: Buffalo CZ]]
[[Category: Hiv]]
[[Category: Hurley JH]]
[[Category: Nef]]
[[Category: Morris KL]]
[[Category: Protein transport]]
[[Category: Ren X]]
[[Category: Trafficking]]
[[Category: Transport protein]]
[[Category: Viral protein]]

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/w/6dff"