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Binding of Gd3+ to the neuronal signalling protein calexcitin identifies an exchangeable Ca2+-binding site

Chataigner, L; Guo, J; Erskine, PT; Coker, AR; Wood, SP; Gombos, Z; Cooper, JB; (2016) Binding of Gd3+ to the neuronal signalling protein calexcitin identifies an exchangeable Ca2+-binding site. Acta Crystallographica Section F: Structural Biology and Crystallization Communications , F72 (4) pp. 276-281. 10.1107/S2053230X16003526. Green open access

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Abstract

Calexcitin was first identified in the marine snail Hermissenda crassicornis as a neuronal-specific protein that becomes upregulated and phosphorylated in associative learning. Calexcitin possesses four EF-hand motifs, but only the first three (EF-1 to EF-3) are involved in binding metal ions. Past work has indicated that under physiological conditions EF-1 and EF-2 bind Mg2+ and Ca2+, while EF-3 is likely to bind only Ca2+. The fourth EF-hand is nonfunctional owing to a lack of key metal-binding residues. The aim of this study was to use a crystallographic approach to determine which of the three metal-binding sites of calexcitin is most readily replaced by exogenous metal ions, potentially shedding light on which of the EF-hands play a `sensory' role in neuronal calcium signalling. By co-crystallizing recombinant calexcitin with equimolar Gd3+ in the presence of trace Ca2+, EF-1 was shown to become fully occupied by Gd3+ ions, while the other two sites remain fully occupied by Ca2+. The structure of the Gd3+-calexcitin complex has been refined to an R factor of 21.5% and an Rfree of 30.4% at 2.2 Å resolution. These findings suggest that EF-1 of calexcitin is the Ca2+-binding site with the lowest selectivity for Ca2+, and the implications of this finding for calcium sensing in neuronal signalling pathways are discussed.

Type: Article
Title: Binding of Gd3+ to the neuronal signalling protein calexcitin identifies an exchangeable Ca2+-binding site
Open access status: An open access version is available from UCL Discovery
DOI: 10.1107/S2053230X16003526
Publisher version: http://doi.org/10.1107/S2053230X16003526
Language: English
Additional information: © 2016 International Union of Crystallography
Keywords: Science & Technology, Life Sciences & Biomedicine, Physical Sciences, Biochemical Research Methods, Biochemistry & Molecular Biology, Biophysics, Crystallography, neuronal calcium signalling, EF-hand, protein structure, heavy-atom complex, co-crystallization, STRUCTURE VALIDATION, DATA QUALITY, KINASE-C, X-RAY, HERMISSENDA, CALCIUM, MEMORY, CRYSTALLIZATION, MODEL, PHOTORECEPTOR
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research
URI: https://discovery.ucl.ac.uk/id/eprint/1481520
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