2cm6

From Proteopedia

Revision as of 16:07, 5 November 2007

CRYSTAL STRUCTURE OF THE C2B DOMAIN OF RABPHILIN3A

Overview

The Ca(2+) binding properties of C2 domains are essential for the function, of their host proteins. We present here the first crystal structures, showing an unexpected Ca(2+) binding mode of the C2B domain of, rabphilin-3A in atomic detail. Acidic residues from the linker region, between the C2A and C2B domains of rabphilin-3A interact with the, Ca(2+)-binding region of the C2B domain. Because of these interactions, the coordination sphere of the two bound Ca(2+) ions is almost complete., Mutation of these acidic residues to alanine resulted in a 10-fold, decrease in the intrinsic Ca(2+) binding affinity of the C2B domain. Using, NMR spectroscopy, we show that this interaction occurred only in the, Ca(2+)-bound state of the C2B domain. In addition, this Ca(2+) binding, mode was maintained in the C2 domain tandem fragment. In NMR-based, liposome binding assays, the linker was not released upon phospholipid, binding. Therefore, this unprecedented Ca(2+) binding mode not only shows, how a C2 domain increases its intrinsic Ca(2+) affinity, but also provides, the structural base for an atypical protein-Ca(2+)-phospholipid binding, mode of rabphilin-3A.

About this Structure

2CM6 is a Single protein structure of sequence from Rattus norvegicus with CA and PO4 as ligands. Structure known Active Site: AC1. Full crystallographic information is available from OCA.

Reference

The C2A-C2B linker defines the high affinity Ca(2+) binding mode of rabphilin-3A., Montaville P, Schlicker C, Leonov A, Zweckstetter M, Sheldrick GM, Becker S, J Biol Chem. 2007 Feb 16;282(7):5015-25. Epub 2006 Dec 13. PMID:17166855

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