title: The Ca(2+) influence on calmodulin unfolding pathway: a steered molecular dynamics simulation study.
abstract: The force-induced unfolding of calmodulin (CaM) was investigated at atomistic details with steered molecular dynamics. The two isolated CaM domains as well as the full-length CaM were simulated in N-C-terminal pulling scheme, and the isolated N-lobe of CaM was studied specially in two other pulling schemes to test the effect of pulling direction and compare with relevant experiments. Both Ca(2+)-loaded CaM and Ca(2+)-free CaM were considered in order to define the Ca(2+) influence to the CaM unfolding. The results reveal that the Ca(2+) significantly affects the stability and unfolding behaviors of both the isolated CaM domains and the full-length CaM. In Ca(2+)-loaded CaM, N-terminal domain unfolds in priori to the C-terminal domain. But in Ca(2+)-free CaM, the unfolding order changes, and C-terminal domain unfolds first. The force-extension curves of CaM unfolding indicate that the major unfolding barrier comes from conquering the interaction of two EF-hand motifs in both N- and C- terminal domains. Our results provide the atomistic-level insights in the force-induced CaM unfolding and explain the observation in recent AFM experiments.
authors.affiliation: Laboratory of Non-Coding RNAs, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jizhong
authors.initials: J
authors.lastname: Lou
mesh_terms: D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D002147:Calmodulin / Q000737:chemistry / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D017510:Protein Folding; D017434:Protein Structure, Tertiary
chemical_list: D002147:Calmodulin; D002118:Calcium