2RLT

phosphorylated CPI-17 (22-120)

Summary for 2RLT

• Entry DOI: 10.2210/pdb2rlt/pdb
• Related: 1J2M 1J2N
• Descriptor: Protein phosphatase 1 regulatory subunit 14A (1 entity in total)
• Functional Keywords: phosphorylation, pp1 inhibitor, cytoplasm, protein phosphatase inhibitor, hydrolase
• Biological source: Sus scrofa (Pig)
• Cellular location: Cytoplasm: O18734
• Total number of polymer chains: 1
• Total formula weight: 11626.06

Authors

Eto, M. (deposition date: 2007-08-11, release date: 2008-07-15, Last modification date: 2024-11-20)

Primary citation

Eto, M.,Kitazawa, T.,Matsuzawa, F.,Aikawa, S.,Kirkbride, J.A.,Isozumi, N.,Nishimura, Y.,Brautigan, D.L.,Ohki, S.Y.
Phosphorylation-induced conformational switching of CPI-17 produces a potent myosin phosphatase inhibitor.
Structure, 15:1591-1602, 2007

PubMed Abstract: 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.

PubMed: 18073109
DOI: 10.1016/j.str.2007.10.014

Experimental method

SOLUTION NMR