The X-ray structure of human calbindin-D28K: an improved model
| Autor: | S. Mark Roe, James W. Noble, John R. Atack, Armin Wagner, Rehab Almalki, Ramona Duman |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
QD0901 Magnetic Resonance Spectroscopy QP0551 Protein Conformation Protein Data Bank (RCSB PDB) chemistry.chemical_element Crystal structure Calcium Calbindin 03 medical and health sciences chemistry.chemical_compound long wavelength 0302 clinical medicine X-Ray Diffraction calbindin Structural Biology mental disorders Scattering Small Angle Animals Humans Inositol EF Hand Motifs Protein secondary structure calcium Binding Sites Chemistry Small-angle X-ray scattering digestive oral and skin physiology calcium SAD Research Papers Protein tertiary structure Rats 3. Good health 030104 developmental biology nervous system calbindin-D28K Calbindin 1 Biophysics 030217 neurology & neurosurgery |
| Zdroj: | Acta Crystallographica. Section D, Structural Biology |
| ISSN: | 2059-7983 |
| Popis: | The X-ray structure of human calbindin-D28K, a calcium-buffering protein that is highly expressed in the central nervous system, is reported. 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. |
| Databáze: | OpenAIRE |
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