title: The conformational plasticity of calmodulin upon calcium complexation gives a model of its interaction with the oedema factor of Bacillus anthracis.
abstract: We analyzed the conformational plasticity of calmodulin (CaM) when it is bound to the oedema factor (EF) of Bacillus anthracis and its response to calcium complexation with molecular dynamics (MD) simulations. The EF-CaM complex was simulated during 15 ns for three different levels of calcium bound to CaM. They were respectively no calcium ion (EF-(Apo-CaM)), two calcium ions bound to the C-terminal domain of CaM (EF-(2Ca-CaM)), and four calcium ions bound to CaM (EF-(4Ca-CaM)). Calculations were performed using AMBER package. The analysis of the MD simulations illustrates how CaM forces EF in an open conformation to form the adenylyl cyclase enzymatic site, especially with the two calcium form of CaM, best suited to fit the open conformation of EF. By contrast, CaM encounters bending and unwinding of its flexible interlinker in EF-(Apo-CaM) and EF-(4Ca-CaM). Calcium binding to one domain of CaM affects the other one, showing a transmission of information along the protein structure. The analysis of the CaM domains conformation along the simulations brings an atomistic and dynamic explanation for the instability of these complexes. Indeed the EF-hand helices of the N-terminal domain tend to open upon calcium binding (EF-(4Ca-CaM)), although the domain is locked by EF. By contrast, the C-terminal domain is strongly locked in the open conformation by EF, and the removal of calcium induces a collapse of EF catalytic site (EF-(Apo-CaM)).
authors.affiliation: Unité de Bioinformatique Structurale, CNRS URA 2185 Institut Pasteur, 25-28, rue du Dr. Roux, Paris 75 724, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Laine
authors.forename: Julliane D
authors.initials: JD
authors.lastname: Yoneda
authors.forename: Arnaud
authors.initials: A
authors.lastname: Blondel
authors.forename: Thérèse E
authors.initials: TE
authors.lastname: Malliavin
mesh_terms: D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000378:metabolism*; D001408:Bacillus anthracis / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D001427:Bacterial Toxins / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000737:chemistry / Q000378:metabolism*; D003198:Computer Simulation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011312:Pressure; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D055672:Static Electricity; D013696:Temperature; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D002147:Calmodulin; C030325:anthrax toxin; D014867:Water; D002118:Calcium