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

DOI: 10.1107/S2059798318011610 DOI Help

Authors: James W. Noble (University Of Sussex) , Rehab Almalki (University Of Sussex) , S. Mark Roe (University Of Sussex) , Armin Wagner (Diamond Light Source) , Ramona Duman (Diamond Light Source) , John Atack (Cardiff University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Acta Crystallographica Section D Structural Biology , VOL 74 , PAGES 1008 - 1014

State: Published (Approved)
Published: October 2018
Diamond Proposal Number(s): 14891 , 11175

Open Access Open Access

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.

Journal Keywords: calbindin; calcium; calbindin-D28K; long wavelength; calcium SAD

Diamond Keywords: Bipolar Disorder

Subject Areas: Biology and Bio-materials


Instruments: B21-High Throughput SAXS , I03-Macromolecular Crystallography , I23-Long wavelength MX

Added On: 08/10/2018 13:58

Documents:
jc5014.pdf

Discipline Tags:

Life Sciences & Biotech Health & Wellbeing Neurology Non-Communicable Diseases Structural biology

Technical Tags:

Diffraction Scattering Macromolecular Crystallography (MX) Small Angle X-ray Scattering (SAXS) Long Wavelength Crystallography