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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Union of Crystallography
2018
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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. |
format | Online Article Text |
id | pubmed-6173056 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | International Union of Crystallography |
record_format | MEDLINE/PubMed |
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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