6jlh
From Proteopedia
Structure of SCGN in complex with a Snap25 peptide
Structural highlights
Function[SNP25_HUMAN] t-SNARE involved in the molecular regulation of neurotransmitter release. May play an important role in the synaptic function of specific neuronal systems. Associates with proteins involved in vesicle docking and membrane fusion. Regulates plasma membrane recycling through its interaction with CENPF. Publication 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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