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

Noble, James William, Almalki, Rehab, Roe, Mark, Duman, Ramona, Wagner, Armin and Atack, John (2018) The X-ray structure of human calbindin-D28K: an improved model. Acta Crystallographica Section D: Structural Biology, 74 (10). pp. 1008-1014. ISSN 2059-7983

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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. Smallangle 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 calbindinD28K 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
Schools and Departments: School of Life Sciences > Biochemistry
Research Centres and Groups: Sussex Drug Discovery Centre
Subjects: Q Science > QD Chemistry > QD0901 Crystallography
Q Science > QP Physiology > QP0501 Animal biochemistry > QP0551 Proteins, amino acids, etc.
Depositing User: James William Noble
Date Deposited: 12 Oct 2018 13:56
Last Modified: 15 Jul 2019 10:00
URI: http://sro.sussex.ac.uk/id/eprint/79457

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Project NameSussex Project NumberFunderFunder Ref
Developing novel pharmacological tools to probe the function of inositol monophosphataseG1668BBSRC-BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCILBB/M017265/1
Developing novel pharmacological tools to probe the function of inositol monophosphataseG1777JANSSEN PHARMACEUTICA NVUnset