title: Sequence motifs determine structure and Ca++-binding by EF-hand proteins.
abstract: Prediction of protein structural and functional characteristics based on specific motif interactions could serve as a powerful tool in many facets of the biological sciences. Such improvements in protein modeling will be instrumental in the enhancement of drug design. A new approach to a sequence description of EF-hand motifs with more than one EF-hand domain is presented here; this permits precise insight into the structural and functional properties of many members of the EF-hand superfamily of calcium-binding proteins. Three separate regular expressions, or signatures, are used to describe an EF-hand motif, and specific relationships must exist between the two sequence motifs for the two neighboring EF-hands in a given calcium-binding domain. Specifically, each of the sequence motifs has a conserved phenylalanine. These two phenylalanine residues are separated by 57+/-10 amino acid residues but interact closely with each other in the tertiary structure of the calcium-binding domain. Changes in conserved residues in the sequence motifs have been shown experimentally to decrease or eliminate the ability of the protein to bind calcium. This new approach of use of multiple sequence motifs, with motif interrelationships, yields a highly specific and robust tool for the prediction of structural and functional properties of new and novel proteins.
authors.affiliation: Department of Biology, University of California, San Diego, La Jolla 92093, USA.
authors.forename: H H
authors.initials: HH
authors.lastname: Rashidi
authors.forename: M
authors.initials: M
authors.lastname: Bauer
authors.forename: J
authors.initials: J
authors.lastname: Patterson
authors.forename: D W
authors.initials: DW
authors.lastname: Smith
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D002147:Calmodulin / Q000737:chemistry; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010649:Phenylalanine; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D002135:Calcium-Binding Proteins; D002147:Calmodulin; D010649:Phenylalanine; D002118:Calcium