Department of Biochemistry and Molecular Pharmacology; Department of Scientific and Research Computing
Biochemistry | Bioinformatics | Cellular and Molecular Physiology | Molecular Biology | Structural Biology | Systems Biology
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.
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Copyright 2014 Mruk et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (seehttp://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described athttp://creativecommons.org/licenses/by-nc-sa/3.0/).
DOI of Published Version
Mruk K, Farley BM, Ritacco AW, Kobertz WR. Calmodulation meta-analysis: Predicting calmodulin binding via canonical motif clustering. J Gen Physiol. 2014 Jun 16. doi:10.1085/jgp.201311140. Link to article on publisher's website
The Journal of general physiology
Mruk, Karen; Farley, Brian M.; Ritacco, Alan W.; and Kobertz, William R., "Calmodulation meta-analysis: Predicting calmodulin binding via canonical motif clustering" (2014). Biochemistry and Molecular Pharmacology Publications and Presentations. 161.