title: PEP-19 modulates calcium binding to calmodulin by electrostatic steering.
abstract: PEP-19 is a small protein that increases the rates of Ca2+binding to the C-domain of calmodulin (CaM) by an unknown mechanism. Although an IQ motif promotes binding to CaM, an acidic sequence in PEP-19 is required to modulate Ca2+binding and to sensitize HeLa cells to ATP-induced Ca2+release. Here, we report the NMR solution structure of a complex between PEP-19 and the C-domain of apo CaM. The acidic sequence of PEP-19 associates between helices E and F of CaM via hydrophobic interactions. This allows the acidic side chains in PEP-19 to extend toward the solvent and form a negatively charged surface that resembles a catcher's mitt near Ca2+binding loop III of CaM. The topology and gradients of negative electrostatic surface potential support a mechanism by which PEP-19 increases the rate of Ca2+binding to the C-domain of CaM by 'catching' and electrostatically steering Ca2+to site III.
authors.affiliation: Department of Biochemistry and Molecular Biology, McGovern Medical at UTHealth, 6431 Fannin, Houston, Texas 77030, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, McGovern Medical at UTHealth, 6431 Fannin, Houston, Texas 77030, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Putkey
mesh_terms: D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D002147:Calmodulin; D009419:Nerve Tissue Proteins; C050394:PCP4 protein, human; D002118:Calcium