Cooperative cyclic interactions involved in metal binding to pairs of sites in EF‐hand proteins

FEBS Letters

Biekofsky, Rodolfo R¹  Feeney, James¹ 

[1] Molecular Structure Division, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK

关键词: Calcium binding protein;    EF-hand pair;    Calmodulin;    Cooperativity;    15N nuclear magnetic resonance;    Semi-empirical quantum mechanics;   

DOI  :  10.1016/S0014-5793(98)01349-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

This study focuses on a closed net of electron-pair donor–acceptor interactions, present in the core of all metal-bound EF-hand pairs, that link both metal ions across a short two-stranded β-sheet. A molecular model based on the above cycle of interactions was studied using semi-empirical molecular orbital quantum mechanical methods. The calculations indicate that the interactions in the model cycle are cooperative, that is, that the interaction energy of the cyclic structure is greater than that of the sum of isolated interactions between its components. The cooperativity in this cycle can be attributed to an increase in the stability of the interactions resulting from a mutual polarisation of the associated groups. The predicted polarisation of the amide groups in the cycle is in agreement with experimental NMR ¹⁵N deshielding observed for these amide groups upon metal binding. Experimental observations of strengthening of the β-sheet hydrogen bonds are also consistent with the model calculations. By this mechanism, the binding of the first metal ion would enhance the binding of the second metal ion, and thus, the intradomain cooperativity in cation binding of calmodulin and related EF-hand proteins can be ascribed, at least partly, to this short-range molecular mechanism.

【 授权许可】

Unknown