4N3Y

Crystal structure of Rabex-5CC and Rabaptin-5C21 complex

Summary for 4N3Y

• Entry DOI: 10.2210/pdb4n3y/pdb
• Related: 4N3X 4N3Z
• Descriptor: Rab5 GDP/GTP exchange factor, Rab GTPase-binding effector protein 1 (3 entities in total)
• Functional Keywords: rab5, rabex-5, rabaptin-5, gef activity, endocytosis, early endosome
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm : Q9UJ41 Q15276
• Total number of polymer chains: 3
• Total formula weight: 26664.03

Authors

Zhang, Z.,Zhang, T.,Ding, J. (deposition date: 2013-10-08, release date: 2014-07-23, Last modification date: 2023-11-08)

Primary citation

Zhang, Z.,Zhang, T.,Wang, S.,Gong, Z.,Tang, C.,Chen, J.,Ding, J.
Molecular mechanism for Rabex-5 GEF activation by Rabaptin-5
Elife, 3:e02687-e02687, 2014

PubMed Abstract: Rabex-5 and Rabaptin-5 function together to activate Rab5 and further promote early endosomal fusion in endocytosis. The Rabex-5 GEF activity is autoinhibited by the Rabex-5 CC domain (Rabex-5CC) and activated by the Rabaptin-5 C2-1 domain (Rabaptin-5C21) with yet unknown mechanism. We report here the crystal structures of Rabex-5 in complex with the dimeric Rabaptin-5C21 (Rabaptin-5C212) and in complex with Rabaptin-5C212 and Rab5, along with biophysical and biochemical analyses. We show that Rabex-5CC assumes an amphipathic α-helix which binds weakly to the substrate-binding site of the GEF domain, leading to weak autoinhibition of the GEF activity. Binding of Rabaptin-5C21 to Rabex-5 displaces Rabex-5CC to yield a largely exposed substrate-binding site, leading to release of the GEF activity. In the ternary complex the substrate-binding site of Rabex-5 is completely exposed to bind and activate Rab5. Our results reveal the molecular mechanism for the regulation of the Rabex-5 GEF activity.

PubMed: 24957337
DOI: 10.7554/eLife.02687

Experimental method

X-RAY DIFFRACTION (2.2 Å)