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1w16

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Revision as of 15:16, 5 November 2007 by OCA (Talk | contribs)
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1w16, resolution 2.30Å

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RAT SYNAPTOTAGMIN 4 C2B DOMAIN IN THE ABSENCE OF CALCIUM

Overview

The neuronal protein synaptotagmin 1 functions as a Ca(2+) sensor in, exocytosis via two Ca(2+)-binding C(2) domains. The very similar, synaptotagmin 4, which includes all the predicted Ca(2+)-binding residues, in the C(2)B domain but not in the C(2)A domain, is also thought to, function as a neuronal Ca(2+) sensor. Here we show that, unexpectedly, both C(2) domains of fly synaptotagmin 4 exhibit Ca(2+)-dependent, phospholipid binding, whereas neither C(2) domain of rat synaptotagmin 4, binds Ca(2+) or phospholipids efficiently. Crystallography reveals that, changes in the orientations of critical Ca(2+) ligands, and perhaps their, flexibility, render the rat synaptotagmin 4 C(2)B domain unable to form, full Ca(2+)-binding sites. These results indicate that synaptotagmin 4 is, a Ca(2+) sensor in the fly but not in the rat, that the Ca(2+)-binding, properties of C(2) domains cannot be reliably predicted from sequence, analyses, and that proteins clearly identified as orthologs may, nevertheless have markedly different functional properties.

About this Structure

1W16 is a Single protein structure of sequence from Rattus norvegicus with NA and CL as ligands. Structure known Active Site: AC1. Full crystallographic information is available from OCA.

Reference

Structural basis for the evolutionary inactivation of Ca2+ binding to synaptotagmin 4., Dai H, Shin OH, Machius M, Tomchick DR, Sudhof TC, Rizo J, Nat Struct Mol Biol. 2004 Sep;11(9):844-9. Epub 2004 Aug 15. PMID:15311271

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