6JLH

Structure of SCGN in complex with a Snap25 peptide

Summary for 6JLH

• Entry DOI: 10.2210/pdb6jlh/pdb
• Descriptor: Secretagogin, Synaptosomal-associated protein 25, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: vesicle transport, endosomal sorting, membrane fusion, protein transport
• Biological source: Danio rerio (Zebrafish); More
• Total number of polymer chains: 4
• Total formula weight: 65905.99

Authors

Qin, J.,Sun, Q.,Jia, D. (deposition date: 2019-03-05, release date: 2020-03-11, Last modification date: 2024-10-09)

Primary citation

Qin, J.,Liu, Q.,Liu, Z.,Pan, Y.Z.,Sifuentes-Dominguez, L.,Stepien, K.P.,Wang, Y.,Tu, Y.,Tan, S.,Wang, Y.,Sun, Q.,Mo, X.,Rizo, J.,Burstein, E.,Jia, D.
Structural and mechanistic insights into secretagogin-mediated exocytosis.
Proc.Natl.Acad.Sci.USA, 117:6559-6570, 2020

PubMed Abstract: Secretagogin (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-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.

PubMed: 32156735
DOI: 10.1073/pnas.1919698117

Experimental method

X-RAY DIFFRACTION (2.37 Å)