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| | <SX load='6owt' size='340' side='right' viewer='molstar' caption='[[6owt]], [[Resolution|resolution]] 3.80Å' scene=''> | | <SX load='6owt' size='340' side='right' viewer='molstar' caption='[[6owt]], [[Resolution|resolution]] 3.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6owt]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat], [http://en.wikipedia.org/wiki/Cerat Cerat] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OWT OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6OWT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6owt]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Cercocebus_atys Cercocebus atys], [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus], [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] and [https://en.wikipedia.org/wiki/Simian_immunodeficiency_virus Simian immunodeficiency virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OWT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OWT FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Ap2a2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), Ap2b1, Clapb1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), Ap2m1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), nef ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9531 CERAT]), Ap2s1, Ap17, Claps2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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]] 3.8Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6owt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6owt OCA], [http://pdbe.org/6owt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6owt RCSB], [http://www.ebi.ac.uk/pdbsum/6owt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6owt 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=6owt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6owt OCA], [https://pdbe.org/6owt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6owt RCSB], [https://www.ebi.ac.uk/pdbsum/6owt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6owt ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/AP2B1_RAT AP2B1_RAT]] Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. The AP-2 beta subunit acts via its C-terminal appendage domain as a scaffolding platform for endocytic accessory proteins; at least some clathrin-associated sorting proteins (CLASPs) are recognized by their [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif. The AP-2 beta subunit binds to clathrin heavy chain, promoting clathrin lattice assembly; clathrin displaces at least some CLASPs from AP2B1 which probably then can be positioned for further coat assembly (By similarity).<ref>PMID:14745134</ref> <ref>PMID:15473838</ref> [[http://www.uniprot.org/uniprot/AP2S1_RAT AP2S1_RAT]] Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein Transport via Transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. The AP-2 alpha and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif. May also play a role in extracellular calcium homeostasis (By similarity).<ref>PMID:14745134</ref> <ref>PMID:15473838</ref> | + | [https://www.uniprot.org/uniprot/AP2A2_RAT AP2A2_RAT] Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. The AP-2 alpha subunit binds polyphosphoinositide-containing lipids, positioning AP-2 on the membrane. The AP-2 alpha subunit acts via its C-terminal appendage domain as a scaffolding platform for endocytic accessory proteins. The AP-2 alpha and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif (By similarity).<ref>PMID:14745134</ref> <ref>PMID:15473838</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6owt" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6owt" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[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: Buffalo rat]] | + | [[Category: Cercocebus atys]] |
| - | [[Category: Cerat]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Buffalo, C Z]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Hurley, J H]] | + | [[Category: Simian immunodeficiency virus]] |
| - | [[Category: Ren, X]] | + | [[Category: Buffalo CZ]] |
| - | [[Category: Ap]] | + | [[Category: Hurley JH]] |
| - | [[Category: Hiv]] | + | [[Category: Ren X]] |
| - | [[Category: Nef]]
| + | |
| - | [[Category: Protein transport]]
| + | |
| - | [[Category: Trafficking]]
| + | |
| - | [[Category: Viral restriction factor]]
| + | |
| Structural highlights
Function
AP2A2_RAT Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. The AP-2 alpha subunit binds polyphosphoinositide-containing lipids, positioning AP-2 on the membrane. The AP-2 alpha subunit acts via its C-terminal appendage domain as a scaffolding platform for endocytic accessory proteins. The AP-2 alpha and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif (By similarity).[1] [2]
Publication Abstract from PubMed
Tetherin is a host defense factor that physically prevents virion release from the plasma membrane. The Nef accessory protein of simian immunodeficiency virus (SIV) engages the clathrin adaptor AP-2 to downregulate tetherin via its DIWK motif. As human tetherin lacks DIWK, antagonism of tetherin by Nef is a barrier to simian-human transmission of non-human primate lentiviruses. To determine the molecular basis for tetherin counteraction, we reconstituted the AP-2 complex with a simian tetherin and SIV Nef and determined its structure by cryoelectron microscopy (cryo-EM). Nef refolds the first alpha-helix of the beta2 subunit of AP-2 to a beta hairpin, creating a binding site for the DIWK sequence. The tetherin binding site in Nef is distinct from those of most other Nef substrates, including MHC class I, CD3, and CD4 but overlaps with the site for the restriction factor SERINC5. This structure explains the dependence of SIVs on tetherin DIWK and consequent barrier to human transmission.
Structural Basis for Tetherin Antagonism as a Barrier to Zoonotic Lentiviral Transmission.,Buffalo CZ, Sturzel CM, Heusinger E, Kmiec D, Kirchhoff F, Hurley JH, Ren X Cell Host Microbe. 2019 Sep 11;26(3):359-368.e8. doi: 10.1016/j.chom.2019.08.002., Epub 2019 Aug 22. PMID:31447307[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Nakatsu F, Ohno H. Adaptor protein complexes as the key regulators of protein sorting in the post-Golgi network. Cell Struct Funct. 2003 Oct;28(5):419-29. PMID:14745134
- ↑ Owen DJ, Collins BM, Evans PR. Adaptors for clathrin coats: structure and function. Annu Rev Cell Dev Biol. 2004;20:153-91. PMID:15473838 doi:10.1146/annurev.cellbio.20.010403.104543
- ↑ Buffalo CZ, Sturzel CM, Heusinger E, Kmiec D, Kirchhoff F, Hurley JH, Ren X. Structural Basis for Tetherin Antagonism as a Barrier to Zoonotic Lentiviral Transmission. Cell Host Microbe. 2019 Sep 11;26(3):359-368.e8. doi: 10.1016/j.chom.2019.08.002., Epub 2019 Aug 22. PMID:31447307 doi:http://dx.doi.org/10.1016/j.chom.2019.08.002
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