A molecular dynamics study of the effect of Ca2+ removal on calmodulin structure.
Calmodulin is a small (148 residues), ubiquitous, highly-conserved Ca(2+) binding protein serving as a modulator of many calcium-dependent processes. In this study, we followed, by means of molecular dynamics, the structural stability of the protein when one of its four bound Ca(2+) ions is removed, and compared it to a simulation of the fully Ca(2+) bound protein. We found that the removal of a single Ca(2+) ion from the N-lobe of the protein, which has a lower affinity for the ion, is sufficient to initiate a considerable structural rearrangement. Although the overall structure of the fully 4 Ca(2+) bound protein remained intact in the extended conformation, the Ca(2+)-removed protein changed its conformation into a compact state. The observation that the 3 Ca(2+) loaded protein assumes a compacted solution state is in accord with experimental observation that the NSCP protein, which binds only three Ca(2+) ions, is natively in a compact state. Examination of the folding dynamics reveals a cooperation between the C-lobe, N-lobe, and the interdomain helix that enable the conformation change. The forces driving this conformational change are discussed.
Laser Laboratory for Fast Reactions in Biology Biochemistry, Tel Aviv University, 69978 Tel Aviv, Israel.
Elad
E
Project
Ran
R
Friedman
Esther
E
Nachliel
Menachem
M
Gutman
D000818:Animals; D002118:Calcium / Q000737:chemistry* / Q000378:metabolism; D002147:Calmodulin / Q000737:chemistry* / Q000378:metabolism; D002413:Cations, Divalent; D003198:Computer Simulation; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding
D002147:Calmodulin; D002413:Cations, Divalent; D002118:Calcium