S3 - Unimore SEMINAR Yongli Zhang

Foto: Prof. Yongli Zhang [courtesy Yale School of Medicine]


Modena - 06.05.2019 - S3 - Unimore SEMINAR Yongli Zhang
Date and Time: May 6, 2019 - 14.30
Venue: S3 Seminar Room, Third Floor, Physics Building, FIM Department

Speaker: Prof. Yongli Zhang
Department of Cell Biology,Yale University School of Medicine, New Haven, CT 06520, USA

Title: SNARE folding and assembly in neurotransmission

Abstract:SNARE proteins and Sec1/Munc18 (SM) proteins constitute the core molecular engine that drives nearly all intracellular membrane fusion and exocytosis. While SNAREs are known to couple their folding and assembly to membrane fusion, the physiological pathway of SNARE assembly and the mechanistic role(s) of SM proteins have long been enigmatic. Using single-molecule force spectroscopy, we found that the SM protein Munc18-1 catalyzes step-wise zippering of three synaptic SNAREs (syntaxin, VAMP2, and SNAP-25) into a four-helix bundle. Catalysis requires formation of an intermediate template complex in which Munc18-1 juxtaposes the N-terminal regions of the SNARE motifs of syntaxin and VAMP2, while keeping their C-terminal regions separated. The template complex is relatively weak, with an unfolding energy of 3.1 kcal/mol, and is stabilized by the N-terminal regulatory domain (NRD) of syntaxin. SNAP-25 binds the templated SNAREs to induce full SNARE zippering. Munc18-1 and SNARE mutations modulate the stability of the template complex in a manner consistent with their effects on membrane fusion, indicating that chaperoned SNARE assembly is essential for exocytosis. Two other SM proteins, Munc18-3 and Vps33, similarly chaperone SNARE assembly via a template complex, suggesting that SM protein mechanism is conserved.

Host: Ciro Cecconi


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