title: Probing the Ca2+/CaM-induced secondary structural and conformational changes in calcineurin.
abstract: Calcineurin (CN) is a Ca(2+)/CaM-dependent Ser/Thr protein phosphatase that plays a critical role in coupling Ca(2+) signals to a cellular response. Various methods have been applied to explore CN activation. A widely accepted model involves CaM binding to the CaM-binding domain (CN 389-413), inducing displacement of the CN autoinhibitory peptide (CN 467-486) from the active site. However, almost the entire regulatory region (CN 374-521), except the autoinhibitory peptide, is not visible in the electron density map of the reported structures. In the present study, we determined the overall secondary structure of CN in the presence or absence of Ca(2+)/CaM using FT-IR, and the Ca(2+)/CaM-induced structural dynamics and conformational changes were monitored by hydrogen-deuterium exchange experiments. The results revealed that the regulatory domain possessed some intrinsic structure. The binding of Ca(2+) and subsequent binding of CaM generated a sequential folding of CN, transforming it into a more constrained, less flexible conformation.
authors.affiliation: Department of Chemistry, Fudan University, Shanghai 200433, China.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Chemistry, Fudan University, Shanghai 200433, China.
authors.forename: Huayan
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Chemistry, Fudan University, Shanghai 200433, China.
authors.forename: Kejie
authors.initials: K
authors.lastname: Meng
authors.affiliation: Department of Chemistry, Fudan University, Shanghai 200433, China. Electronic address: yushaoning@fudan.edu.cn.
authors.forename: Shaoning
authors.initials: S
authors.lastname: Yu
mesh_terms: D019703:Calcineurin / Q000737:chemistry*; D002118:Calcium / Q000737:chemistry*; D002147:Calmodulin / Q000737:chemistry*; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D002147:Calmodulin; D011994:Recombinant Proteins; D019703:Calcineurin; D002118:Calcium
keywords: Calcineurin; Calcium; Calmodulin