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

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posted on 2023-06-09, 15:28 authored by James Noble, Rehab Almalki, Mark Roe, Ramona Duman, Armin Wagner, John Atack
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.

Funding

Developing novel pharmacological tools to probe the function of inositol monophosphatase; G1668; BBSRC-BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCIL; BB/M017265/1

Developing novel pharmacological tools to probe the function of inositol monophosphatase; G1777; JANSSEN PHARMACEUTICA NV

History

Publication status

  • Published

File Version

  • Published version

Journal

Acta Crystallographica Section D: Structural Biology

ISSN

2059-7983

Publisher

International Union of Crystallography

Issue

10

Volume

74

Page range

1008-1014

Department affiliated with

  • Biochemistry Publications

Research groups affiliated with

  • Sussex Drug Discovery Centre Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2018-10-12

First Open Access (FOA) Date

2018-10-12

First Compliant Deposit (FCD) Date

2018-10-11

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