4M8M

Crystal structure of the active dimer of zebrafish PlexinC1 cytoplasmic region

Summary for 4M8M

• Entry DOI: 10.2210/pdb4m8m/pdb
• Related: 4M8N
• Descriptor: GCN4 coiled-coil fused zebrafish PlexinC1 (2 entities in total)
• Functional Keywords: rasgap-like fold, gap for rap gtpases, rap, membrane, signaling protein
• Biological source: Danio rerio (leopard danio,zebra danio,zebra fish)
• Total number of polymer chains: 2
• Total formula weight: 146247.38

Authors

Wang, Y.,Pascoe, H.G.,Zhang, X. (deposition date: 2013-08-13, release date: 2013-10-09, Last modification date: 2024-02-28)

Primary citation

Wang, Y.,Pascoe, H.G.,Brautigam, C.A.,He, H.,Zhang, X.
Structural basis for activation and non-canonical catalysis of the Rap GTPase activating protein domain of plexin.
Elife, 2:e01279-e01279, 2013

PubMed Abstract: Plexins are cell surface receptors that bind semaphorins and transduce signals for regulating neuronal axon guidance and other processes. Plexin signaling depends on their cytoplasmic GTPase activating protein (GAP) domain, which specifically inactivates the Ras homolog Rap through an ill-defined non-canonical catalytic mechanism. The plexin GAP is activated by semaphorin-induced dimerization, the structural basis for which remained unknown. Here we present the crystal structures of the active dimer of zebrafish PlexinC1 cytoplasmic region in the apo state and in complex with Rap. The structures show that the dimerization induces a large-scale conformational change in plexin, which opens the GAP active site to allow Rap binding. Plexin stabilizes the switch II region of Rap in an unprecedented conformation, bringing Gln63 in Rap into the active site for catalyzing GTP hydrolysis. The structures also explain the unique Rap-specificity of plexins. Mutational analyses support that these mechanisms underlie plexin activation and signaling. DOI:http://dx.doi.org/10.7554/eLife.01279.001.

PubMed: 24137545
DOI: 10.7554/eLife.01279

Experimental method

X-RAY DIFFRACTION (3.307 Å)