Taken together, our findings allow us to model the orientation of Ric1-Rgp1 on the Golgi membrane and understand how it activates Rab6. (9/10)

Ryan also identified a conserved amphipathic alpha-helix within Rgp1 that is flexibly linked to the bulk of the complex and likely plays a role in membrane binding. Removal of this helix significantly reduces the Golgi localization of the complex in cells. (8/10)

Our lab previously determined that two other RabGEF complexes, TRAPPII and TRAPPIII, also use the HVDs of their substrates as specificity determinants, suggesting that HVD binding may be common among GEFs. (7/10)

Surprisingly, C-terminal HVD of Rab6 binds to a conserved surface of the Rgp1 arrestin fold. We found the HVD sequence is important for activation in cells and also for nucleotide exchange catalyzed by Ric1-Rgp1 in vitro, indicating that binding to the HVD is important for Ric1-Rgp1 function. (6/10)

Ryan identified key residues in the GEF domain and found they are essential for GEF activity in an in vitro reconstitution system utilizing purified proteins, prenylated Rab6-GDI substrate, and synthetic liposome membranes. (5/10)

The Ric1 subunit possesses a novel GEF domain that dramatically remodels the Rab6 nucleotide binding site to release GDP. (4/10)

@ryanfeathers.bsky.social used #cryoEM to determine the structural basis of the Rab6 activation process. Ryan’s structure reveals the architecture of the complex and provides a mechanistic explanation for Ric1-Rgp1 function. (3/10)

Excited to share the published version of our work by @ryanfeathers.bsky.social and @rvig.bsky.social on the structural basis for activation of Rab6 by the Ric1-Rgp1 complex! rdcu.be/d2mu3

Here is an updated thread about the paper we first shared on that older platform when we posted the preprint