title: The conformation of calmodulin: a substantial environmentally sensitive helical transition in Ca4-calmodulin with potential mechanistic function.
abstract: The conformation of Ca4-calmodulin in solution, as assessed by far-UV peptide circular dichroism, contains significantly less alpha-helix than the proposed X-ray crystal structure. We now show that Ca4-calmodulin adopts significant additional helical structure in solution in the presence of a helicogenic solvent (50%, v/v, aqueous 2,2,2-trifluoroethanol or 50%, v/v, methylpentane-5,5-diol). We suggest that the long continuous helix (residues 66-92 of the crystal structure) is not necessarily a normal feature of the calmodulin structure in solution, and may be due in part to the conditions of crystallisation. This result is supported by time-resolved tyrosine fluorescence anisotropy studies indicating that Ca4-calmodulin in solution is an essentially compact globular structure which undergoes isotropic rotational motion. We conclude that, under appropriate ionic and apolar environmental conditions, Ca4-calmodulin undergoes a substantial helical transition, which may involve residues in the central region of the molecule. Such a transition could have an important function in determining specificity and affinity in interactions of calmodulin with different target sequences of Ca2+-dependent regulatory enzymes.
authors.affiliation: Division of Physical Biochemistry, National Institute for Medical Research, Mill Hill, London, England.
authors.forename: P
authors.initials: P
authors.lastname: Bayley
authors.forename: S
authors.initials: S
authors.lastname: Martin
authors.forename: G
authors.initials: G
authors.lastname: Jones
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism*; D002417:Cattle; D002942:Circular Dichroism; D005454:Fluorescence Polarization; D007700:Kinetics; D008297:Male; D011485:Protein Binding; D011487:Protein Conformation; D013737:Testis / Q000378:metabolism; D014961:X-Ray Diffraction
chemical_list: D002147:Calmodulin; D002118:Calcium