Melittin binding causes a large calcium-dependent conformational change in calmodulin.
The interaction between calmodulin and its target protein is a key step in many calcium-regulated cellular functions. Melittin binds tightly to calmodulin in the presence of calcium and is a competitive inhibitor of calmodulin function. Using melittin as a model for the target peptide of calmodulin, we have found a large Ca2+-dependent conformational change of calmodulin in solution induced by peptide binding. Mg2+ does not substitute for Ca2+ in producing the conformation change. Small-angle x-ray scattering has shown that calmodulin exists as a dumbbell in solution, similar to that observed in the crystalline state. Our present measurements reveal that the overall structure of the Ca2+-calmodulin-melittin complex is not a dumbbell but a globular shape. Upon binding melittin, the radius of gyration decreases from 20.9 to 18.0 A and the largest dimension decreases from 60 to 47.5 A. In the absence of calcium, however, melittin has little effect on the solution structure of calmodulin.
Kataoka
M
M
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511.
Head
J F
JF
Seaton
B A
BA
Engelman
D M
DM
D000818:Animals; D001514:Bee Venoms / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology*; D002147:Calmodulin / Q000378:metabolism*; D002417:Cattle; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008555:Melitten / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D011487:Protein Conformation; D014961:X-Ray Diffraction
D001514:Bee Venoms; D002147:Calmodulin; D008555:Melitten; D008274:Magnesium; D002118:Calcium