title: Calmodulation meta-analysis: predicting calmodulin binding via canonical motif clustering.
abstract: The calcium-binding protein calmodulin (CaM) directly binds to membrane transport proteins to modulate their function in response to changes in intracellular calcium concentrations. Because CaM recognizes and binds to a wide variety of target sequences, identifying CaM-binding sites is difficult, requiring intensive sequence gazing and extensive biochemical analysis. Here, we describe a straightforward computational script that rapidly identifies canonical CaM-binding motifs within an amino acid sequence. Analysis of the target sequences from high resolution CaM-peptide structures using this script revealed that CaM often binds to sequences that have multiple overlapping canonical CaM-binding motifs. The addition of a positive charge discriminator to this meta-analysis resulted in a tool that identifies potential CaM-binding domains within a given sequence. To allow users to search for CaM-binding motifs within a protein of interest, perform the meta-analysis, and then compare the results to target peptide-CaM structures deposited in the Protein Data Bank, we created a website and online database. The availability of these tools and analyses will facilitate the design of CaM-related studies of ion channels and membrane transport proteins.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology and Programs in Chemical Biology and Neuroscience, and.
authors.forename: Karen
authors.initials: K
authors.lastname: Mruk
authors.affiliation: Department of Biochemistry and Molecular Pharmacology and Programs in Chemical Biology and Neuroscience, and.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Farley
authors.affiliation: Department of Scientific and Research Computing, University of Massachusetts Medical School, Worcester, MA 01605.
authors.forename: Alan W
authors.initials: AW
authors.lastname: Ritacco
authors.affiliation: Department of Biochemistry and Molecular Pharmacology and Programs in Chemical Biology and Neuroscience, and william.kobertz@umassmed.edu.
authors.forename: William R
authors.initials: WR
authors.lastname: Kobertz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002147:Calmodulin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D016000:Cluster Analysis; D005544:Forecasting; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000502:physiology; D017433:Protein Structure, Secondary
chemical_list: D002147:Calmodulin