2cjs

Structural Basis for a Munc13-1 Homodimer - Munc13-1 - RIM Heterodimer Switch: C2-domains as Versatile Protein-Protein Interaction Modules

spinqualitylabelsall models 2cjs, resolution 1.78Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2cjs is a 3 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EDO, GOL, ZN Related: 1y8f, 2a20, 2bwq, 2cjt Resources: FirstGlance, OCA, RCSB, PDBsum Function [RIMS2_RAT] Rab effector involved in exocytosis. May act as scaffold protein. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed C(2) domains are well characterized as Ca(2+)/phospholipid-binding modules, but little is known about how they mediate protein-protein interactions. In neurons, a Munc13-1 C(2)A-domain/RIM zinc-finger domain (ZF) heterodimer couples synaptic vesicle priming to presynaptic plasticity. We now show that the Munc13-1 C(2)A domain homodimerizes, and that homodimerization competes with Munc13-1/RIM heterodimerization. X-ray diffraction studies guided by nuclear magnetic resonance (NMR) experiments reveal the crystal structures of the Munc13-1 C(2)A-domain homodimer and the Munc13-1 C(2)A-domain/RIM ZF heterodimer at 1.44 A and 1.78 A resolution, respectively. The C(2)A domain adopts a beta-sandwich structure with a four-stranded concave side that mediates homodimerization, leading to the formation of an eight-stranded beta-barrel. In contrast, heterodimerization involves the bottom tip of the C(2)A-domain beta-sandwich and a C-terminal alpha-helical extension, which wrap around the RIM ZF domain. Our results describe the structural basis for a Munc13-1 homodimer-Munc13-1/RIM heterodimer switch that may be crucial for vesicle priming and presynaptic plasticity, uncovering at the same time an unexpected versatility of C(2) domains as protein-protein interaction modules, and illustrating the power of combining NMR spectroscopy and X-ray crystallography to study protein complexes. Structural basis for a Munc13-1 homodimer to Munc13-1/RIM heterodimer switch.,Lu J, Machius M, Dulubova I, Dai H, Sudhof TC, Tomchick DR, Rizo J PLoS Biol. 2006 Jul;4(7):e192. PMID:16732694 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA