8BBJ

Secretagogin (mouse) in complex with its target peptide from Syntaxin-4

8BBJ の概要

• エントリーDOI: 10.2210/pdb8bbj/pdb
• 分子名称: Green fluorescent protein,Syntaxin-4, Secretagogin, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: calcium dependent, protein complex, peptide binding protein
• 由来する生物種: Aequorea victoria; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 103320.29

構造登録者

Schnell, R.,Szodorai, E. (登録日: 2022-10-13, 公開日: 2024-04-03, 最終更新日: 2024-11-13)

主引用文献

Szodorai, E.,Hevesi, Z.,Wagner, L.,Hokfelt, T.G.M.,Harkany, T.,Schnell, R.
A hydrophobic groove in secretagogin allows for alternate interactions with SNAP-25 and syntaxin-4 in endocrine tissues.
Proc.Natl.Acad.Sci.USA, 121:e2309211121-e2309211121, 2024

PubMed Abstract: Vesicular release of neurotransmitters and hormones relies on the dynamic assembly of the exocytosis/trans-SNARE complex through sequential interactions of synaptobrevins, syntaxins, and SNAP-25. Despite SNARE-mediated release being fundamental for intercellular communication in all excitable tissues, the role of auxiliary proteins modulating the import of reserve vesicles to the active zone, and thus, scaling repetitive exocytosis remains less explored. Secretagogin is a Ca-sensor protein with SNAP-25 being its only known interacting partner. SNAP-25 anchors readily releasable vesicles within the active zone, thus being instrumental for 1st phase release. However, genetic deletion of secretagogin impedes 2nd phase release instead, calling for the existence of alternative protein-protein interactions. Here, we screened the secretagogin interactome in the brain and pancreas, and found syntaxin-4 grossly overrepresented. Ca-loaded secretagogin interacted with syntaxin-4 at nanomolar affinity and 1:1 stoichiometry. Crystal structures of the protein complexes revealed a hydrophobic groove in secretagogin for the binding of syntaxin-4. This groove was also used to bind SNAP-25. In mixtures of equimolar recombinant proteins, SNAP-25 was sequestered by secretagogin in competition with syntaxin-4. K differences suggested that secretagogin could shape unidirectional vesicle movement by sequential interactions, a hypothesis supported by in vitro biological data. This mechanism could facilitate the movement of transport vesicles toward release sites, particularly in the endocrine pancreas where secretagogin, SNAP-25, and syntaxin-4 coexist in both α- and β-cells. Thus, secretagogin could modulate the pace and fidelity of vesicular hormone release by differential protein interactions.

PubMed: 38593081
DOI: 10.1073/pnas.2309211121

実験手法

X-RAY DIFFRACTION (2.65 Å)