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Structure of SCGN in complex with a Snap25 peptideStructure of SCGN in complex with a Snap25 peptide
Structural highlights
FunctionPublication Abstract from PubMedSecretagogin (SCGN) is a hexa-EF-hand protein that is highly expressed in the pancreas, brain, and gastrointestinal tract. SCGN is known to modulate regulated exocytosis in multiple cell lines and tissues; however, its exact functions and underlying mechanisms remain unclear. Here, we report that SCGN interacts with the plasma membrane SNARE SNAP-25, but not the assembled SNARE complex, in a Ca(2+)-dependent manner. The crystal structure of SCGN in complex with a SNAP-25 fragment reveals that SNAP-25 adopts a helical structure and binds to EF-hands 5 and 6 of SCGN. SCGN strongly inhibits SNARE-mediated vesicle fusion in vitro by binding to SNAP-25. SCGN promotes the plasma membrane localization of SNAP-25, but not Syntaxin-1a, in SCGN-expressing cells. Finally, SCGN controls neuronal growth and brain development in zebrafish, likely via interacting with SNAP-25 or its close homolog, SNAP-23. Our results thus provide insights into the regulation of SNAREs and suggest that aberrant synapse functions underlie multiple neurological disorders caused by SCGN deficiency. Structural and mechanistic insights into secretagogin-mediated exocytosis.,Qin J, Liu Q, Liu Z, Pan YZ, Sifuentes-Dominguez L, Stepien KP, Wang Y, Tu Y, Tan S, Wang Y, Sun Q, Mo X, Rizo J, Burstein E, Jia D Proc Natl Acad Sci U S A. 2020 Mar 24;117(12):6559-6570. doi:, 10.1073/pnas.1919698117. Epub 2020 Mar 10. PMID:32156735[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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