1w15

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==Overview==
==Overview==
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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.
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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==
==About this Structure==
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[[Category: Machius, M.]]
[[Category: Machius, M.]]
[[Category: Rizo, J.]]
[[Category: Rizo, J.]]
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[[Category: Shin, O.H.]]
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[[Category: Shin, O H.]]
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[[Category: Sudhof, T.C.]]
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[[Category: Sudhof, T C.]]
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[[Category: Tomchick, D.R.]]
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[[Category: Tomchick, D R.]]
[[Category: CA]]
[[Category: CA]]
[[Category: CL]]
[[Category: CL]]
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[[Category: transmembrane]]
[[Category: transmembrane]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 10:17:57 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:39:22 2008''

Revision as of 13:39, 21 February 2008


1w15, resolution 1.93Å

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RAT SYNAPTOTAGMIN 4 C2B DOMAIN IN THE PRESENCE 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

1W15 is a Single protein structure of sequence from Rattus norvegicus with , and as ligands. Known structural/functional Site: . 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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