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

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, inosi...

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Autores principales: Noble, James W., Almalki, Rehab, Roe, S. Mark, Wagner, Armin, Duman, Ramona, Atack, John R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Union of Crystallography 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173056/
https://www.ncbi.nlm.nih.gov/pubmed/30289411
http://dx.doi.org/10.1107/S2059798318011610
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author Noble, James W.
Almalki, Rehab
Roe, S. Mark
Wagner, Armin
Duman, Ramona
Atack, John R.
author_facet Noble, James W.
Almalki, Rehab
Roe, S. Mark
Wagner, Armin
Duman, Ramona
Atack, John R.
author_sort Noble, James W.
collection PubMed
description 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.
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spelling pubmed-61730562018-10-12 The X-ray structure of human calbindin-D28K: an improved model Noble, James W. Almalki, Rehab Roe, S. Mark Wagner, Armin Duman, Ramona Atack, John R. Acta Crystallogr D Struct Biol Research Papers 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. International Union of Crystallography 2018-10-02 /pmc/articles/PMC6173056/ /pubmed/30289411 http://dx.doi.org/10.1107/S2059798318011610 Text en © Noble et al. 2018 http://creativecommons.org/licenses/by/2.0/uk/ This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.http://creativecommons.org/licenses/by/2.0/uk/
spellingShingle Research Papers
Noble, James W.
Almalki, Rehab
Roe, S. Mark
Wagner, Armin
Duman, Ramona
Atack, John R.
The X-ray structure of human calbindin-D28K: an improved model
title The X-ray structure of human calbindin-D28K: an improved model
title_full The X-ray structure of human calbindin-D28K: an improved model
title_fullStr The X-ray structure of human calbindin-D28K: an improved model
title_full_unstemmed The X-ray structure of human calbindin-D28K: an improved model
title_short The X-ray structure of human calbindin-D28K: an improved model
title_sort x-ray structure of human calbindin-d28k: an improved model
topic Research Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173056/
https://www.ncbi.nlm.nih.gov/pubmed/30289411
http://dx.doi.org/10.1107/S2059798318011610
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