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4nee

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Revision as of 22:07, 5 August 2016

crystal structure of AP-2 alpha/simga2 complex bound to HIV-1 Nef

Structural highlights

4nee is a 12 chain structure with sequence from 9hiv1 and Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Gene:	Ap2s1, Ap17, Claps2 (Buffalo rat), Ap17, Ap2a2, Ap2s1, Claps2 (Buffalo rat), nef (9HIV1)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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).^[1] ^[2]

Publication Abstract from PubMed

The Nef protein of HIV-1 downregulates the cell surface co-receptor CD4 by hijacking the clathrin adaptor complex AP-2. The structural basis for the hijacking of AP-2 by Nef is revealed by a 2.9 A crystal structure of Nef bound to the alpha and sigma2 subunits of AP-2. Nef binds to AP-2 via its central loop (residues 149-179) and its core. The determinants for Nef binding include residues that directly contact AP-2 and others that stabilize the binding-competent conformation of the central loop. Residues involved in both direct and indirect interactions are required for the binding of Nef to AP-2 and for downregulation of CD4. These results lead to a model for the docking of the full AP-2 tetramer to membranes as bound to Nef, such that the cytosolic tail of CD4 is situated to interact with its binding site on Nef. DOI: http://dx.doi.org/10.7554/eLife.01754.001.

How HIV-1 Nef hijacks the AP-2 clathrin adaptor to downregulate CD4.,Ren X, Park SY, Bonifacino JS, Hurley JH Elife. 2014;3:e01754. doi: 10.7554/eLife.01754. Epub 2014 Jan 1. PMID:24473078^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Ren X, Park SY, Bonifacino JS, Hurley JH. How HIV-1 Nef hijacks the AP-2 clathrin adaptor to downregulate CD4. Elife. 2014;3:e01754. doi: 10.7554/eLife.01754. Epub 2014 Jan 1. PMID:24473078 doi:http://dx.doi.org/10.7554/eLife.01754

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4nee"

@@ Line 1: / Line 1: @@
 ==crystal structure of AP-2 alpha/simga2 complex bound to HIV-1 Nef==
 <StructureSection load='4nee' size='340' side='right' caption='[[4nee]], [[Resolution|resolution]] 2.88&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Ap2s1, Ap17, Claps2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), Ap17, Ap2a2, Ap2s1, Claps2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), nef ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 9HIV1])</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=4nee FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nee OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4nee RCSB], [http://www.ebi.ac.uk/pdbsum/4nee PDBsum]</span></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=4nee FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nee OCA], [http://pdbe.org/4nee PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4nee RCSB], [http://www.ebi.ac.uk/pdbsum/4nee PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4nee ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4nee" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Adaptin|Adaptin]]
 == References ==
 <references/>

4nee

From Proteopedia

Revision as of 22:07, 5 August 2016

crystal structure of AP-2 alpha/simga2 complex bound to HIV-1 Nef

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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