6DJL

Crystal structure of the Rab11 GEF SH3BP5 bound to nucleotide free Rab11A

Summary for 6DJL

• Entry DOI: 10.2210/pdb6djl/pdb
• Descriptor: Ras-related protein Rab-11A, SH3 domain-binding protein 5 (2 entities in total)
• Functional Keywords: rab gtpase, guanine nucleotide exchange factor, membrane trafficking, protein transport, signaling protein-protein transport complex, signaling protein/protein transport
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 222895.27

Authors

Burke, J.E.,Jenkins, M.L.,Boulanger, M.J. (deposition date: 2018-05-25, release date: 2018-09-26, Last modification date: 2024-03-13)

Primary citation

Jenkins, M.L.,Margaria, J.P.,Stariha, J.T.B.,Hoffmann, R.M.,McPhail, J.A.,Hamelin, D.J.,Boulanger, M.J.,Hirsch, E.,Burke, J.E.
Structural determinants of Rab11 activation by the guanine nucleotide exchange factor SH3BP5.
Nat Commun, 9:3772-3772, 2018

PubMed Abstract: The GTPase Rab11 plays key roles in receptor recycling, oogenesis, autophagosome formation, and ciliogenesis. However, investigating Rab11 regulation has been hindered by limited molecular detail describing activation by cognate guanine nucleotide exchange factors (GEFs). Here, we present the structure of Rab11 bound to the GEF SH3BP5, along with detailed characterization of Rab-GEF specificity. The structure of SH3BP5 shows a coiled-coil architecture that mediates exchange through a unique Rab-GEF interaction. Furthermore, it reveals a rearrangement of the switch I region of Rab11 compared with solved Rab-GEF structures, with a constrained conformation when bound to SH3BP5. Mutation of switch I provides insights into the molecular determinants that allow for Rab11 selectivity over evolutionarily similar Rab GTPases present on Rab11-positive organelles. Moreover, we show that GEF-deficient mutants of SH3BP5 show greatly decreased Rab11 activation in cellular assays of active Rab11. Overall, our results give molecular insight into Rab11 regulation, and how Rab-GEF specificity is achieved.

PubMed: 30217979
DOI: 10.1038/s41467-018-06196-z

Experimental method

X-RAY DIFFRACTION (3.10001148084 Å)