1W16

rat synaptotagmin 4 C2B domain in the absence of calcium

Summary for 1W16

• Entry DOI: 10.2210/pdb1w16/pdb
• Related: 1W15
• Descriptor: SYNAPTOTAGMIN IV, SODIUM ION, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: metal binding protein, synaptotagmin, endocytosis/exocytosis, neurotransmitter release, transmembrane
• Biological source: RATTUS NORVEGICUS (RAT)
• Total number of polymer chains: 1
• Total formula weight: 16914.25

Authors

Dai, H.,Shin, O.-H.,Machius, M.,Tomchick, D.R.,Sudhof, T.C.,Rizo, J. (deposition date: 2004-06-16, release date: 2004-08-13, Last modification date: 2023-12-13)

Primary citation

Dai, H.,Shin, O.-H.,Machius, M.,Tomchick, D.R.,Sudhof, T.C.,Rizo, J.
Structural Basis for the Evolutionary Inactivation of Ca2+ Binding to Synaptotagmin 4
Nat.Struct.Mol.Biol., 11:844-, 2004

PubMed Abstract: 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.

PubMed: 15311271
DOI: 10.1038/NSMB817

Experimental method

X-RAY DIFFRACTION (2.3 Å)