A cryo-EM structure of metazoan TRAPPIII, the multisubunit complex that activates the GTPase Rab1

ABSTRACT: The TRAPP complexes are nucleotide exchange factors that have essential roles in membrane traffic and autophagy. TRAPPII activates Rab11, and TRAPPIII activates Rab1, with the two complexes sharing a core of small subunits that affect nucleotide exchange, but being distinguished by specific large subunits that are essential for activity in vivo. Crystal structures of core subunits have revealed the mechanism of Rab activation, but how the core and the large subunits assemble to form the complexes was unknown. We report a cryo-EM structure of the entire TRAPPIII complex from Drosophila. The TRAPPIII-specific subunits TRAPPC8 and TRAPPC11 hold the catalytic core like a pair of tongs, with TRAPPC12 and TRAPPC13 positioned at the joint between them. TRAPPC2 and TRAPPC2L link the core to the two large arms, with the interfaces containing residues affected by disease-causing mutations. The TRAPPC8 arm is positioned such that it would contact Rab1 that is bound to the core, indicating how the arm could determine the specificity of the complex. A lower resolution structure of TRAPPII shows a similar architecture, and suggests that the TRAPP complexes evolved from a single ur-TRAPP.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Drosophila Melanogaster (fruit Fly)

SUBMITTER: Mark Skehel  

LAB HEAD: Sean Munro

PROVIDER: PXD025064 | Pride | 2021-06-03

REPOSITORIES: Pride