2rlt

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phosphorylated CPI-17 (22-120)

Structural highlights

2rlt is a 1 chain structure with sequence from Sus scrofa. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR, 1 model
Ligands:TPO
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PP14A_PIG Inhibitor of PPP1CA. Has over 1000-fold higher inhibitory activity when phosphorylated, creating a molecular switch for regulating the phosphorylation status of PPP1CA substrates and smooth muscle contraction.[1] [2] [3] [4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Phosphorylation of endogenous inhibitor proteins for type-1 Ser/Thr phosphatase (PP1) provides a mechanism for reciprocal coordination of kinase and phosphatase activities. A myosin phosphatase inhibitor protein CPI-17 is phosphorylated at Thr38 through G-protein-mediated signals, resulting in a >1000-fold increase in inhibitory potency. We show here the solution NMR structure of phospho-T38-CPI-17 with rmsd of 0.36 +/- 0.06 A for the backbone secondary structure, which reveals how phosphorylation triggers a conformational change and exposes an inhibitory surface. This active conformation is stabilized by the formation of a hydrophobic core of intercalated side chains, which is not formed in a phospho-mimetic D38 form of CPI-17. Thus, the profound increase in potency of CPI-17 arises from phosphorylation, conformational change, and hydrophobic stabilization of a rigid structure that poses the phosphorylated residue on the protein surface and restricts its hydrolysis by myosin phosphatase. Our results provide structural insights into transduction of kinase signals by PP1 inhibitor proteins.

Phosphorylation-induced conformational switching of CPI-17 produces a potent myosin phosphatase inhibitor.,Eto M, Kitazawa T, Matsuzawa F, Aikawa S, Kirkbride JA, Isozumi N, Nishimura Y, Brautigan DL, Ohki SY Structure. 2007 Dec;15(12):1591-602. PMID:18073109[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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See Also

References

  1. ↑ Eto M, Senba S, Morita F, Yazawa M. Molecular cloning of a novel phosphorylation-dependent inhibitory protein of protein phosphatase-1 (CPI17) in smooth muscle: its specific localization in smooth muscle. FEBS Lett. 1997 Jun 30;410(2-3):356-60. PMID:9237662
  2. ↑ Eto M, Ohmori T, Suzuki M, Furuya K, Morita F. A novel protein phosphatase-1 inhibitory protein potentiated by protein kinase C. Isolation from porcine aorta media and characterization. J Biochem. 1995 Dec;118(6):1104-7. PMID:8720121
  3. ↑ Hamaguchi T, Ito M, Feng J, Seko T, Koyama M, Machida H, Takase K, Amano M, Kaibuchi K, Hartshorne DJ, Nakano T. Phosphorylation of CPI-17, an inhibitor of myosin phosphatase, by protein kinase N. Biochem Biophys Res Commun. 2000 Aug 11;274(3):825-30. PMID:10924361 doi:http://dx.doi.org/10.1006/bbrc.2000.3225
  4. ↑ Koyama M, Ito M, Feng J, Seko T, Shiraki K, Takase K, Hartshorne DJ, Nakano T. Phosphorylation of CPI-17, an inhibitory phosphoprotein of smooth muscle myosin phosphatase, by Rho-kinase. FEBS Lett. 2000 Jun 23;475(3):197-200. PMID:10869555
  5. ↑ Eto M, Kitazawa T, Matsuzawa F, Aikawa S, Kirkbride JA, Isozumi N, Nishimura Y, Brautigan DL, Ohki SY. Phosphorylation-induced conformational switching of CPI-17 produces a potent myosin phosphatase inhibitor. Structure. 2007 Dec;15(12):1591-602. PMID:18073109 doi:10.1016/j.str.2007.10.014

Contents


PDB ID 2rlt

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