9AYR

Structure of a Ric1-Rgp1-Rab6 activation intermediate

Summary for 9AYR

• Entry DOI: 10.2210/pdb9ayr/pdb
• EMDB information: 43997
• Descriptor: Guanine nucleotide exchange factor subunit RIC1, Guanine nucleotide exchange factor subunit RGP1, GTP-binding protein YPT6 (3 entities in total)
• Functional Keywords: gef, gtpase, rab, protein transport
• Biological source: Saccharomyces cerevisiae (brewer's yeast); More
• Total number of polymer chains: 3
• Total formula weight: 219344.88

Authors

Feathers, J.R.,Fromme, J.C. (deposition date: 2024-03-08, release date: 2024-12-11, Last modification date: 2025-05-28)

Primary citation

Feathers, J.R.,Vignogna, R.C.,Fromme, J.C.
Structural basis for Rab6 activation by the Ric1-Rgp1 complex.
Nat Commun, 15:10561-10561, 2024

PubMed Abstract: Rab GTPases act as molecular switches to regulate organelle homeostasis and membrane trafficking. Rab6 plays a central role in regulating cargo flux through the Golgi and is activated via nucleotide exchange by the Ric1-Rgp1 protein complex. Ric1-Rgp1 is conserved throughout eukaryotes but the structural and mechanistic basis for its function has not been established. Here we report the cryoEM structure of a Ric1-Rgp1-Rab6 complex representing a key intermediate of the nucleotide exchange reaction. Ric1-Rgp1 interacts with the nucleotide-binding domain of Rab6 using an uncharacterized helical domain, which we establish as a RabGEF domain by identifying residues required for Rab6 activation. Unexpectedly, the complex uses an arrestin fold to interact with the Rab6 hypervariable domain, indicating that interactions with the unstructured C-terminal regions of Rab GTPases may be a common binding mechanism used by their activators. Collectively, our findings provide a detailed mechanistic understanding of regulated Rab6 activation at the Golgi.

PubMed: 39632878
DOI: 10.1038/s41467-024-54869-9

Experimental method

ELECTRON MICROSCOPY (3.3 Å)