title: A renewed model of CNA regulation involving its C-terminal regulatory domain and CaM.
abstract: Calcineurin is composed of a catalytic subunit (CNA) and a regulatory subunit (CNB). CNA contains the catalytic domain and three regulatory domains: a CNB-binding domain (BBH), a C-terminal calmodulin-binding domain (CBD), and an autoinhibitory domain (AID). We constructed a series of mutants of CNA to explore the regulatory role of its C-terminal regulatory domain and CaM. We demonstrated a more precise mechanism of CNA regulation by C-terminal residues 389-511 in the presence of CNB. First, we showed that residues 389-413, which were identified in previous work as constituting a CaM binding domain (CBD), also have an autoinhibiting function. We also found that residues 389-413 were not sufficient for CaM binding and that the CBD comprises at least residues 389-456. In conclusion, two distinct segments of the C-terminal regulatory region (389-511) of CNA inhibit enzyme activity: residues 389-413 interact with the CNB binding helix (BBH), and residues 457-482 with the active center of CNA.
authors.affiliation: Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, Beijing 100875, PR China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Wang
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Du
authors.forename: Benqiong
authors.initials: B
authors.lastname: Xiang
authors.forename: Weilin
authors.initials: W
authors.lastname: Lin
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Qun
authors.initials: Q
authors.lastname: Wei
mesh_terms: D001665:Binding Sites; D019703:Calcineurin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002147:Calmodulin / Q000737:chemistry*; D020134:Catalytic Domain; D004791:Enzyme Inhibitors / Q000737:chemistry; D007700:Kinetics; D008954:Models, Biological; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D010455:Peptides / Q000737:chemistry; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D002147:Calmodulin; D004791:Enzyme Inhibitors; D010455:Peptides; D021122:Protein Subunits; D019703:Calcineurin