title: Structure of calmodulin bound to a calcineurin peptide: a new way of making an old binding mode.
abstract: Calcineurin is a calmodulin-binding protein in brain and the only serine/threonine protein phosphatase under the control of Ca2+/calmodulin (CaM), which plays a critical role in coupling Ca2+ signals to cellular responses. CaM up-regulates the phosphatase activity of calcineurin by binding to the CaM-binding domain (CBD) of calcineurin subunit A. Here, we report crystal structural studies of CaM bound to a CBD peptide. The chimeric protein containing CaM and the CBD peptide forms an intimate homodimer, in which CaM displays a native-like extended conformation and the CBD peptide shows alpha-helical structure. Unexpectedly, the N-terminal lobe from one CaM and the C-terminal lobe from the second molecule form a combined binding site to trap the peptide. Thus, the dimer provides two binding sites, each of which is reminiscent of the fully collapsed conformation of CaM commonly observed in complex with, for example, the myosin light chain kinase (MLCK) peptide. The interaction between the peptide and CaM is highly specific and similar to MLCK.
authors.affiliation: Department of Biochemistry and Molecular Biology, Beijing Key Laboratory, Beijing Normal University, Beijing 100875, People's Republic of China.
authors.forename: Qilu
authors.initials: Q
authors.lastname: Ye
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Andrew
authors.initials: A
authors.lastname: Wong
authors.forename: Qun
authors.initials: Q
authors.lastname: Wei
authors.forename: Zongchao
authors.initials: Z
authors.lastname: Jia
mesh_terms: D000595:Amino Acid Sequence; D019703:Calcineurin / Q000737:chemistry* / Q000378:metabolism*; D002147:Calmodulin / Q000737:chemistry* / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics; D013816:Thermodynamics
chemical_list: D002147:Calmodulin; D011993:Recombinant Fusion Proteins; D019703:Calcineurin