title: Novel calcium recognition constructions in proteins: Calcium blade and EF-hand zone.
abstract: Metal ions can regulate various cell processes being first, second or third messengers, and some of them, especially transition metal ions, take part in catalysis in many enzymes. As an intracellular ion, Ca2+is involved in many cellular functions from fertilization and contraction, cell differentiation and proliferation, to apoptosis and cancer. Here, we have identified and described two novel calcium recognition environments in proteins: the calcium blade zone and the EF-hand zone, common to 12 and 8 different protein families, respectively. Each of the two environments contains three distinct structural elements: (a) the well-known characteristic Dx[DN]xDG motif; (b) an adjacent structurally identical segment, which binds metal ion in the same way between the calcium blade zone and the EF-hand zone; and (c) the following structurally variable segment, which distinguishes the calcium blade zone from the EF-hand zone. Both zones have sequence insertions between the last residue of the zone and calcium-binding residues in positions V or VI. The long insertion often connects the active and the calcium-binding sites in proteins. Using the structurally identical segments as an anchor, we were able to construct the classical calmodulin type EF-hand calcium-binding site out of two different calcium-binding motifs from two unrelated proteins.
authors.affiliation: Faculty of Science and Engineering, Åbo Akademi University, Turku 20500, Finland; Institute for Biological Instrumentation of the Russian Academy of Sciences, Pushchino 142290, Russia. Electronic address: adenesyu@abo.fi.
authors.forename: Alexander I
authors.initials: AI
authors.lastname: Denesyuk
authors.affiliation: Institute for Biological Instrumentation of the Russian Academy of Sciences, Pushchino 142290, Russia.
authors.forename: Sergei E
authors.initials: SE
authors.lastname: Permyakov
authors.affiliation: Faculty of Science and Engineering, Åbo Akademi University, Turku 20500, Finland.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Johnson
authors.affiliation: Institute for Biological Instrumentation of the Russian Academy of Sciences, Pushchino 142290, Russia.
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Permyakov
authors.affiliation: Molecular Plant Biology, Department of Biochemistry, University of Turku, Turku 20520, Finland.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Denessiouk
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020832:EF Hand Motifs; D006801:Humans; D008958:Models, Molecular; D016254:Mutagenesis, Insertional; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid
chemical_list: D002135:Calcium-Binding Proteins; D002118:Calcium
keywords: Beta-propeller; Blade; Calcium; EF-hand; Protein structure; Structure motifs