Construction and molecular dynamics simulation of calmodulin in the extended and in a bent conformation.
Analysis of sequence similarity and comparison of the three-dimensional (3D) structures of troponin C and calmodulin have revealed a sequence in the central helix of calmodulin with a high probability for bending. The three amino acids known to form a bend in the N-terminal portion of troponin C are also found in the central helix of calmodulin. The modelling of a bent calmodulin structure, using the dihedral angles of the three residues in the bend of troponin C as a 3D template, results in a conformation of calmodulin where the N- and C-terminal domains are able to form contacts. Dynamics simulations starting from the X-ray structure of calmodulin and from the modelled bent calmodulin were carried out to compare flexibility and correlated movements of Ca2+ in the binding loops. Both conformations of calmodulin remained stable during the period of simulation. In the simulation of calmodulin in the extended form, the motions of the Ca2+ atoms in the two domains (Ca2+1 and Ca2+2 in one domain, and Ca2+3 and Ca2+4 in the other) are correlated. In the simulation of the bent form, an additional correlation between the Ca atoms in the two different domains is observed. The results are compatible with the occurrence of a bent conformation of calmodulin in the presence of targets, and with increased Ca2+ affinity and cooperativity of the Ca(2+)-binding loops in the calmodulin-peptide complexes.
Vorherr
T
T
Institute of Biochemistry, Swiss Federal Institute of Technology, Zurich, Switzerland.
Kessler
O
O
Mark
A
A
Carafoli
E
E
D002118:Calcium / Q000737:chemistry; D002147:Calmodulin / Q000737:chemistry*; D002412:Cations; D011487:Protein Conformation; D014961:X-Ray Diffraction
D002147:Calmodulin; D002412:Cations; D002118:Calcium