3TW8

GEF domain of DENND 1B in complex with Rab GTPase Rab35

Summary for 3TW8

• Entry DOI: 10.2210/pdb3tw8/pdb
• Related: 1YZN 2FOL
• Descriptor: DENN domain-containing protein 1B, Ras-related protein Rab-35 (3 entities in total)
• Functional Keywords: longin domain, rab gtpase, guanine exchange factor, protein transport
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane; Lipid-anchor; Cytoplasmic side (Potential): Q15286
• Total number of polymer chains: 4
• Total formula weight: 129806.04

Authors

Wu, X.D.,Kummel, D.,Reinisch, K.M. (deposition date: 2011-09-21, release date: 2011-11-16, Last modification date: 2024-02-28)

Primary citation

Wu, X.,Bradley, M.J.,Cai, Y.,Kummel, D.,De La Cruz, E.M.,Barr, F.A.,Reinisch, K.M.
Insights regarding guanine nucleotide exchange from the structure of a DENN-domain protein complexed with its Rab GTPase substrate.
Proc.Natl.Acad.Sci.USA, 108:18672-18677, 2011

PubMed Abstract: Rab GTPases are key regulators of membrane traffic pathways within eukaryotic cells. They are specifically activated by guanine nucleotide exchange factors (GEFs), which convert them from their "inactive" GDP-bound form to the "active" GTP-bound form. In higher eukaryotes, proteins containing DENN-domains comprise a major GEF family. Here we describe at 2.1-Å resolution the first structure of a DENN-domain protein, DENND1B-S, complexed with its substrate Rab35, providing novel insights as to how DENN-domain GEFs interact with and activate Rabs. DENND1B-S is bi-lobed, and interactions with Rab35 are through conserved surfaces in both lobes. Rab35 binds via switch regions I and II, around the nucleotide-binding pocket. Positional shifts in Rab residues required for nucleotide binding may lower its affinity for bound GDP, and a conformational change in switch I, which makes the nucleotide-binding pocket more solvent accessible, likely also facilitates exchange.

PubMed: 22065758
DOI: 10.1073/pnas.1110415108

Experimental method

X-RAY DIFFRACTION (2.1 Å)