Annexin A5 D226K structure and dynamics: identification of a molecular switch for the large‐scale conformational change of domain III

FEBS Letters

Russo-Marie, Françoise³  Vincent, Michel²  Gallay, Jacques²  Tabaries, Sébastien³  Lewit-Bentley, Anita²  Kerbœuf, Daniel³  Chevalier, Anne³  Sopkova-De Oliveira Santos, Jana¹ 

[1] UFR des Sciences Pharmaceutiques, 5 rue Vaubenard, F-14032 Caen, France;L.U.R.E. Laboratoire pour l'Utilisation du Rayonnement Electromagnétique, Université Paris-Sud, Bâtiment 209D, P.O. Box 34, F-91898 Orsay Cedex, France;I.C.G.M. U332 INSERM Hôpital Cochin, 22 rue Méchin, F-75014 Paris, France

关键词: Annexin 5;    Calcium- and pH-induced conformational change;    Electrostatic interaction;    X-ray diffraction;    Time-resolved fluorescence;    Tryptophan;    Anx5;    annexin A5;    W187;    tryptophan 187;    T224;    threonine 224;    D226;    aspartic acid 226;    D226K;    mutant of human annexin V where aspartic 226 is replaced by a lysine;    T224V;    mutant of human annexin V where threonine 224 is replaced by a valine;    MEM;    maximum entropy method;   

DOI  :  10.1016/S0014-5793(01)02285-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The domain III of annexin 5 undergoes a Ca²⁺- and a pH-dependent conformational transition of large amplitude. Modeling of the transition pathway by computer simulations suggested that the interactions between D226 and T229 in the IIID–IIIE loop on the one hand and the H-bond interactions between W187 and T224 on the other hand, are important in this process [Sopkova et al. (2000) Biochemistry 39, 14065–14074]. In agreement with the modeling, we demonstrate in this work that the D226K mutation behaves as a molecular switch of the pH- and Ca²⁺-mediated conformational transition. In contrast, the hydrogen bonds between W187 and T224 seem marginal.

【 授权许可】

Unknown