Structural highlights
4m8n is a 8 chain structure with sequence from Brachidanio rerio and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
|
| Ligands: | , , |
| Gene: | Plexin C1, plxnc1 (Brachidanio rerio), OK/SW-cl.11, Rap 1B, RAP1B (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[RAP1B_HUMAN] GTP-binding protein that possesses intrinsic GTPase activity. Contributes to the polarizing activity of KRIT1 and CDH5 in the establishment and maintenance of correct endothelial cell polarity and vascular lumen. Required for the localization of phosphorylated PRKCZ, PARD3 and TIAM1 to the cell junction.[1] [2]
Publication Abstract from PubMed
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.
Structural basis for activation and non-canonical catalysis of the Rap GTPase activating protein domain of plexin.,Wang Y, Pascoe HG, Brautigam CA, He H, Zhang X Elife. 2013 Oct 1;2:e01279. doi: 10.7554/eLife.01279. PMID:24137545[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lampugnani MG, Orsenigo F, Rudini N, Maddaluno L, Boulday G, Chapon F, Dejana E. CCM1 regulates vascular-lumen organization by inducing endothelial polarity. J Cell Sci. 2010 Apr 1;123(Pt 7):1073-80. doi: 10.1242/jcs.059329. PMID:20332120 doi:10.1242/jcs.059329
- ↑ Rehmann H, Arias-Palomo E, Hadders MA, Schwede F, Llorca O, Bos JL. Structure of Epac2 in complex with a cyclic AMP analogue and RAP1B. Nature. 2008 Sep 4;455(7209):124-7. Epub 2008 Jul 27. PMID:18660803 doi:http://dx.doi.org/10.1038/nature07187
- ↑ Wang Y, Pascoe HG, Brautigam CA, He H, Zhang X. Structural basis for activation and non-canonical catalysis of the Rap GTPase activating protein domain of plexin. Elife. 2013 Oct 1;2:e01279. doi: 10.7554/eLife.01279. PMID:24137545 doi:http://dx.doi.org/10.7554/eLife.01279
