6TQT
The crystal structure of the MSP domain of human MOSPD2.
Summary for 6TQT
| Entry DOI | 10.2210/pdb6tqt/pdb |
| Descriptor | Motile sperm domain-containing protein 2, 1,2-ETHANEDIOL, PHOSPHATE ION, ... (4 entities in total) |
| Functional Keywords | membrane contact sites, ffat motif, msp domain, endoplasmic reticulum, protein binding |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 24520.60 |
| Authors | McEwen, A.G.,Poussin-Courmontagne, P.,Di Mattia, T.,Wendling, C.,Cavarelli, J.,Tomasetto, C.,Alpy, F. (deposition date: 2019-12-17, release date: 2020-11-18, Last modification date: 2024-01-24) |
| Primary citation | Di Mattia, T.,Martinet, A.,Ikhlef, S.,McEwen, A.G.,Nomine, Y.,Wendling, C.,Poussin-Courmontagne, P.,Voilquin, L.,Eberling, P.,Ruffenach, F.,Cavarelli, J.,Slee, J.,Levine, T.P.,Drin, G.,Tomasetto, C.,Alpy, F. FFAT motif phosphorylation controls formation and lipid transfer function of inter-organelle contacts. Embo J., 39:e104369-e104369, 2020 Cited by PubMed Abstract: 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. PubMed: 33124732DOI: 10.15252/embj.2019104369 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.5 Å) |
Structure validation
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