title: Residue-residue interactions regulating the Ca2+-induced EF-hand conformation changes in calmodulin.
abstract: Calmodulin (CaM) is a Ca2+-binding messenger protein having four Ca2+-binding motifs named 'EF-hand'; the EF-hand motifs undergo a conformation change induced by Ca2+-binding. In order to study how Ca2+-binding induces the conformation change of EF-hand motifs and which residues are involved in the reaction, two 1μ second long MD simulations were independently performed from the apo- and holo-CaM and their structures and interactions were compared. The Ca2+-binding weakens the helix-helix interaction in all EF-hand, however, the holo-CaM MD adopted the close-like form. The correlation coefficients obtained from the two MDs show the residues comprising interactions being involved in their close-open conformation changes; most of these residues are hydrophobic amino acids but some of them are hydrophilic (T34, H107, N111 and Q143). The hydrophilic residues are expected to lock the EF-hands by their side-chains and main-chain carbonyl oxygen of another hydrophobic residue. Furthermore, the interaction pattern of EF-hand3 and 4 are similar to each other. On the other hand, the interaction pattern of EF-hand2 is different from others; its polar residues are expected to play an important role in regulating the EF-hand2 conformation.
authors.affiliation: School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Shimoyama
authors.affiliation: School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Takeda-Shitaka
mesh_terms: D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D002147:Calmodulin / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation
chemical_list: D002147:Calmodulin; D002118:Calcium
keywords: EF-hand motif; calmodulin; conformation change; molecular dynamics; residue–residue interaction