View source for 6tqr


==The crystal structure of the MSP domain of human VAP-A in complex with the Phospho-FFAT motif of STARD3.==
<StructureSection load='6tqr' size='340' side='right'caption='[[6tqr]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6tqr]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TQR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TQR 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]] 1.85&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</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=6tqr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tqr OCA], [https://pdbe.org/6tqr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tqr RCSB], [https://www.ebi.ac.uk/pdbsum/6tqr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tqr ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/VAPA_HUMAN VAPA_HUMAN] May play a role in vesicle trafficking.<ref>PMID:11511104</ref> <ref>PMID:19289470</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Organelles are physically connected in membrane contact sites. The endoplasmic reticulum possesses three major receptors, VAP-A, VAP-B, and MOSPD2, which interact with proteins at the surface of other organelles to build contacts. VAP-A, VAP-B, and MOSPD2 contain an MSP domain, which binds a motif named FFAT (two phenylalanines in an acidic tract). In this study, we identified a non-conventional FFAT motif where a conserved acidic residue is replaced by a serine/threonine. We show that phosphorylation of this serine/threonine is critical for non-conventional FFAT motifs (named Phospho-FFAT) to be recognized by the MSP domain. Moreover, structural analyses of the MSP domain alone or in complex with conventional and Phospho-FFAT peptides revealed new mechanisms of interaction. Based on these new insights, we produced a novel prediction algorithm, which expands the repertoire of candidate proteins with a Phospho-FFAT that are able to create membrane contact sites. Using a prototypical tethering complex made by STARD3 and VAP, we showed that phosphorylation is instrumental for the formation of ER-endosome contacts, and their sterol transfer function. This study reveals that phosphorylation acts as a general switch for inter-organelle contacts.

FFAT motif phosphorylation controls formation and lipid transfer function of inter-organelle contacts.,Di Mattia T, Martinet A, Ikhlef S, McEwen AG, Nomine Y, Wendling C, Poussin-Courmontagne P, Voilquin L, Eberling P, Ruffenach F, Cavarelli J, Slee J, Levine TP, Drin G, Tomasetto C, Alpy F EMBO J. 2020 Oct 30:e104369. doi: 10.15252/embj.2019104369. PMID:33124732<ref>PMID:33124732</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6tqr" style="background-color:#fffaf0;"></div>

==See Also==
*[[Vesicle-associated membrane protein|Vesicle-associated membrane protein]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Alpy F]]
[[Category: Cavarelli J]]
[[Category: Di Mattia T]]
[[Category: McEwen AG]]
[[Category: Poussin-Courmontagne P]]
[[Category: Tomasetto C]]
[[Category: Wendling C]]