Electrostatics effects on Ca(2+) binding and conformational changes in EF-hand domains: Functional implications for EF-hand proteins.
Mutations of Gln41 and Lys75 with nonpolar residues in the N-terminal domain of calmodulin (N-Cam) revealed the importance of solvation energetics in conformational change of Ca(2+) sensor EF-hand domains. While in general these domains have polar residues at these corresponding positions yet the extent of their conformational response to Ca(2+) binding and their Ca(2+) binding affinity can be different from N-Cam. Consequently, here we address the charge state of the polar residues at these positions. The results show that the charge state of these polar residues can affect substantially the conformational change and the Ca(2+) binding affinity of our N-Cam variants. Since all the variants kept their conformational activity in the presence of Ca(2+) suggests that the differences observed among them mainly originate from the difference in their molecular dynamics. Hence we propose that the molecular dynamics of Ca(2+) sensor EF-hand domains is a key factor in the multifunctional aspect of EF-hand proteins.
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK. Electronic address: a.ababou10@yahoo.co.uk.
Abdessamad
A
Ababou
Cardiovascular and Randall Division, King's College London, Guy's Campus, London SE1 1UL, UK.
Mariola
M
Zaleska
D000595:Amino Acid Sequence; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000737:chemistry* / Q000378:metabolism*; D002413:Cations, Divalent / Q000378:metabolism; D020832:EF Hand Motifs; D006801:Humans; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D055672:Static Electricity; D013816:Thermodynamics
D002147:Calmodulin; D002413:Cations, Divalent; D002118:Calcium
CD and fluorescence spectroscopy; Ca(2+) binding affinity; EF-hand proteins; Electrostatic effect; MD simulation; Protein stability