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

The domain III of annexin 5 undergoes a Ca2+- and a pH-dependent conformati onal transition of large amplitude. Modeling of the transition pathway by c omputer simulations suggested that the interactions between D226 and T229 i n the IIID-IIIE loop on the one hand and the H-bond interactions between W1 87 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 swi tch of the pH- and Ca2+-mediated conformational transition. In contrast, th e hydrogen bonds between W187 and T224 seem marginal. (C) 2001 Federation o f European Biochemical Societies. Published by Elsevier Science B.V. All ri ghts reserved.