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Structural basis of TRAPPIII‐mediated Rab1 activation

DOI: 10.15252/embj.2020107607 DOI Help

Authors: Aaron M. N. Joiner (Cornell University) , Ben P. Phillips (MRC Laboratory of Molecular Biology) , Kumar Yugandhar (Cornell University) , Ethan J Sanford (Cornell University) , Marcus B Smolka (Cornell University) , Haiyuan Yu (Cornell University) , Elizabeth A. Miller (MRC Laboratory of Molecular Biology) , J Christopher Fromme (Cornell University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: The Embo Journal , VOL 74

State: Published (Approved)
Published: May 2021
Diamond Proposal Number(s): 17434

Open Access Open Access

Abstract: The GTPase Rab1 is a master regulator of the early secretory pathway and is critical for autophagy. Rab1 activation is controlled by its guanine nucleotide exchange factor, the multisubunit TRAPPIII complex. Here, we report the 3.7 Å cryo-EM structure of the Saccharomyces cerevisiae TRAPPIII complex bound to its substrate Rab1/Ypt1. The structure reveals the binding site for the Rab1/Ypt1 hypervariable domain, leading to a model for how the complex interacts with membranes during the activation reaction. We determined that stable membrane binding by the TRAPPIII complex is required for robust activation of Rab1/Ypt1 in vitro and in vivo, and is mediated by a conserved amphipathic α-helix within the regulatory Trs85 subunit. Our results show that the Trs85 subunit serves as a membrane anchor, via its amphipathic helix, for the entire TRAPPIII complex. These findings provide a structural understanding of Rab activation on organelle and vesicle membranes.

Subject Areas: Biology and Bio-materials

Diamond Offline Facilities: Electron Bio-Imaging Centre (eBIC)
Instruments: Krios III-Titan Krios III at Diamond

Added On: 24/05/2021 13:05

Documents:
embj.2020107607.pdf

Discipline Tags:

Life Sciences & Biotech Structural biology

Technical Tags:

Microscopy Electron Microscopy (EM) Cryo Electron Microscopy (Cryo EM)