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 Ca(2+)- 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 Ca(2+)-mediated conformational transition. In contrast, the hydrogen bonds between W187 and T224 seem marginal.
Sopkova-De Oliveira Santos
J
J
UFR des Sciences Pharmaceutiques, 5 rue Vaubenard, F-14032 Caen, France.
Vincent
M
M
Tabaries
S
S
Chevalier
A
A
Kerboeuf
D
D
Russo-Marie
F
F
Lewit-Bentley
A
A
Gallay
J
J
D017304:Annexin A5 / Q000737:chemistry* / Q000235:genetics; D002118:Calcium / Q000494:pharmacology; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008958:Models, Molecular; D017354:Point Mutation; D011487:Protein Conformation / Q000187:drug effects; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D055672:Static Electricity; D013816:Thermodynamics
D017304:Annexin A5; D017931:DNA Primers; D011994:Recombinant Proteins; D002118:Calcium