钙结合蛋白D28k的功能及调节异常的蛋白结构分析：Ca2+、Zn2+之间潜在的竞争

Title:Protein Structural Analysis of Calbindin D_28k Function and Dysregulation: Potential Competition Between Ca²⁺ and Zn²⁺

Volume: 13 Issue: 7

Author(s): Sara Ibrahim Omar, Benedict C. Albensi, Kathleen M. Gough

Affiliation:

关键词: 阿尔茨海默病，钙结合蛋白D28k，钙结合蛋白，钙稳态，分子动力学模拟，锌。

摘要: Calcium homeostasis is an essential physiological process requiring tight control in the normal cell. The dysregulation of calcium homeostasis may play a key role in the onset of Alzheimer’s disease (AD) and other disorders, whether through the loss of calcium binding or calcium sensing capacity. Calbindin D_28k (CB-D_28k), a calcium binding protein composed of six EF-hands, four of which can bind Ca²⁺, has been implicated in AD-related calcium dysregulation. In this study, docking and molecular dynamics calculations were employed to refine the protein data base model in order to understand the underlying structural variations between functional and non-functional EF-hands. Molecular modeling calculations improved the modelled protein structure: helix-loop-helix sequences were formed in all hands and most canonical interactions were formed in the four functional hands. The protein can also bind Zn²⁺, potentially altering the Ca²⁺ binding capability. Analysis of calculated structures of Zn²⁺ bound protein showed that only half of the correct EF-hand canonical interactions of Ca²⁺ were formed with loop residues. These results have important implications for the understanding of calcium dysregulation as well as for the development of novel therapeutic strategies in AD and other central nervous system disease processes, or in conditions of brain injury where calcium homeostasis is compromised.

Cite this article as:

Sara Ibrahim Omar, Benedict C. Albensi, Kathleen M. Gough , Protein Structural Analysis of Calbindin D_28k Function and Dysregulation: Potential Competition Between Ca²⁺ and Zn²⁺, Current Alzheimer Research 2016; 13 (7) . https://dx.doi.org/10.2174/1567205013666160310144100