2cjs

File:2cjs.gif

spinqualitylabelsall models 2cjs, resolution 1.78Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D

STRUCTURAL BASIS FOR A MUNC13-1 HOMODIMER- MUNC13-1- RIM HETERODIMER SWITCH: C2-DOMAINS AS VERSATILE PROTEIN-PROTEIN INTERACTION MODULES

Overview

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.

About this Structure

2CJS is a Protein complex structure of sequences from Rattus norvegicus with ZN, EDO and GOL as ligands. Structure known Active Site: AC1. Full crystallographic information is available from OCA.

Reference

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 Jun;4(7):e192. PMID:16732694

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