1k5o
CPI-17(35-120) deletion mutant
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OverviewOverview
Contractility of vascular smooth muscle depends on phosphorylation of, myosin light chains, and is modulated by hormonal control of myosin, phosphatase activity. Signaling pathways activate kinases such as PKC or, Rho-dependent kinases that phosphorylate the myosin phosphatase inhibitor, protein called CPI-17. Phosphorylation of CPI-17 at Thr38 enhances its, inhibitory potency 1000-fold, creating a molecular on/off switch for, regulating contraction. We report the solution NMR structure of the CPI-17, inhibitory domain (residues 35-120), which retains the signature, biological properties of the full-length protein. The final ensemble of 20, sets of NMR coordinates overlaid onto their mean structure with r.m.s.d., values of 0.84(+/-0.22) A for the backbone atoms. The protein forms a, novel four-helix, V-shaped bundle comprised of a central anti-parallel, helix pair (B/C helices) flanked by two large spiral loops formed by the N, and C termini that are held together by another anti-parallel helix pair, (A/D helices) stabilized by intercalated aromatic and aliphatic, side-chains. Chemical shift perturbations indicated that phosphorylation, of Thr38 induces a conformational change involving displacement of helix, A, without significant movement of the other three helices. This, conformational change seems to flex one arm of the molecule, thereby, exposing new surfaces of the helix A and the nearby phosphorylation loop, to form specific interactions with the catalytic site of the phosphatase., This phosphorylation-dependent conformational change offers new structural, insights toward understanding the specificity of CPI-17 for myosin, phosphatase and its function as a molecular switch.
About this StructureAbout this Structure
1K5O is a Single protein structure of sequence from Sus scrofa. Full crystallographic information is available from OCA.
ReferenceReference
Solution NMR structure of the myosin phosphatase inhibitor protein CPI-17 shows phosphorylation-induced conformational changes responsible for activation., Ohki S, Eto M, Kariya E, Hayano T, Hayashi Y, Yazawa M, Brautigan D, Kainosho M, J Mol Biol. 2001 Dec 7;314(4):839-49. PMID:11734001
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