DOI: 10.1110/ps.04832604. Crystallographic identification of Ca2+ and Sr2+ coordination sites in synaptotagmin I C2B domain

Crystallographic identification of Ca2+ and Sr2+ coordination sites in synaptotagmin I C2B domain

10.1110/ps.04832604

Crossref journal-article

Wiley

Protein Science (311)

Abstract

AbstractSynaptotagmin I has two tandem Ca2+‐binding C2 domains, which are essential for fast synchronous synaptic transmission in the central nervous system. We have solved four crystal structures of the C2B domain, one of them in the cation‐free form at 1.50 Å resolution, two in the Ca2+‐bound form at 1.04 Å (two bound Ca2+ ions) and 1.65 Å (three bound Ca2+ ions) resolution and one in the Sr2+‐bound form at 1.18 Å (one bound Sr2+ ion) resolution. The side chains of four highly conserved aspartic acids (D303, D309, D363, and D365) and two main chain oxygens (M302:O and Y364:O), together with water molecules, are in direct contact with two bound Ca2+ ions (sites 1 and 2). At higher Ca2+ concentrations, the side chain of N333 rotates and cooperates with D309 to generate a third Ca2+ coordination site (site 3). Divalent cation binding sites 1 and 2 in the C2B domain were previously identified from NMR NOE patterns and titration studies, supplemented by site‐directed mutation analysis. One difference between the crystal and NMR studies involves D371, which is not involved in coordination with any of the identified Ca2+ sites in the crystal structures, while it is coordinated to Ca2+ in site 2 in the NMR structure. In the presence of Sr2+, which is also capable of triggering exocytosis, but with lower efficiency, only one cation binding site (site 1) was occupied in the crystallographic structure.

Bibliography

Cheng, Y., Sequeira, S. M., Malinina, L., Tereshko, V., SÃ¶llner, T. H., & Patel, D. J. (2004). Crystallographic identification of Ca2+ and Sr2+ coordination sites in synaptotagmin I C2B domain. Protein Science, 13(10), 2665â2672. Portico.

Authors 6

Yuan Cheng (first)
Sonia M. Sequeira (additional)
Lucy Malinina (additional)
Valentina Tereshko (additional)
Thomas H. Söllner (additional)
Dinshaw J. Patel (additional)

References 18 Referenced 56

10.1107/S0907444998003254 / Acta Crystallogr. D Biol. Crystallogr. / Crystallography & NMR system: A new software suite for macro‐molecular structure determination by Brunger A.T. (1998)
10.1107/S0907444994003112
10.1016/S0896-6273(01)00548-7
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10.1073/pnas.91.26.12942
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10.1016/S0896-6273(02)01145-5
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Dates

Type	When
Created	21 years ago (Aug. 31, 2004, 8:24 p.m.)
Deposited	1 year, 10 months ago (Oct. 9, 2023, 3:14 p.m.)
Indexed	2 months ago (July 2, 2025, 2:31 p.m.)
Issued	20 years, 11 months ago (Oct. 1, 2004)
Published	20 years, 11 months ago (Oct. 1, 2004)
Published Online	16 years, 8 months ago (Jan. 1, 2009)
Published Print	20 years, 11 months ago (Oct. 1, 2004)

Funders 0

None

BibTeX

@article{Cheng_2004, title={Crystallographic identification of Ca2+ and Sr2+ coordination sites in synaptotagmin I C2B domain}, volume={13}, ISSN={1469-896X}, url={http://dx.doi.org/10.1110/ps.04832604}, DOI={10.1110/ps.04832604}, number={10}, journal={Protein Science}, publisher={Wiley}, author={Cheng, Yuan and Sequeira, Sonia M. and Malinina, Lucy and Tereshko, Valentina and Söllner, Thomas H. and Patel, Dinshaw J.}, year={2004}, month=oct, pages={2665–2672} }

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