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: | 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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