The X-ray structure of human calbindin-D28K: an improved model

Noble, James W., Almalki, Rehab, Roe, S. Mark, Wagner, Armin, Duman, Ramona and Atack, John R. ORCID: https://orcid.org/0000-0002-3410-791X 2018. The X-ray structure of human calbindin-D28K: an improved model. Acta Crystallographica. Section D: Structural Biology 74 (10) , pp. 1008-1014. 10.1107/S2059798318011610

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Abstract

Calbindin-D28K is a widely expressed calcium-buffering cytoplasmic protein that is involved in many physiological processes. It has been shown to interact with other proteins, suggesting a role as a calcium sensor. Many of the targets of calbindin-D28K are of therapeutic interest: for example, inositol monophos­phatase, the putative target of lithium therapy in bipolar disorder. Presented here is the first crystal structure of human calbindin-D28K. There are significant deviations in the tertiary structure when compared with the NMR structure of rat calbindin-D28K (PDB entry 2g9b), despite 98% sequence identity. Small-angle X-ray scattering (SAXS) indicates that the crystal structure better predicts the properties of calbindin-D28K in solution compared with the NMR structure. Here, the first direct visualization of the calcium-binding properties of calbindin-D28K is presented. Four of the six EF-hands that make up the secondary structure of the protein contain a calcium-binding site. Two distinct conformations of the N-terminal EF-hand calcium-binding site were identified using long-wavelength calcium single-wavelength anomalous dispersion (SAD). This flexible region has previously been recognized as a protein–protein interaction interface. SAXS data collected in both the presence and absence of calcium indicate that there are no large structural differences in the globular structure of calbindin-D28K between the calcium-loaded and unloaded proteins.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Publisher:	International Union of Crystallography
ISSN:	2059-7983
Date of First Compliant Deposit:	19 December 2018
Date of Acceptance:	16 August 2018
Last Modified:	05 May 2023 02:40
URI:	https://orca.cardiff.ac.uk/id/eprint/117783

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