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Please use this identifier to cite or link to this item: http://hdl.handle.net/10119/7870

Title: Phosphorylation-Induced Conformational Switching of CPI-17 Produces a Potent Myosin Phosphatase Inhibitor
Authors: Eto, Masumi
Kitazawa, Toshio
Matsuzawa, Fumiko
Aikawa, Sei-ichi
Kirkbride, Jason A.
Isozumi, Noriyoshi
Nishimura, Yumi
Brautigan, David L.
Ohki, Shin-ya
Keywords: PROTEINS
SIGNALING
Issue Date: 2007-12-13
Publisher: Elsevier
Magazine name: Structure
Volume: 15
Number: 12
Start page: 1591
End page: 1602
DOI: 10.1016/j.str.2007.10.014
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 at Thr38 is phosphorylated 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 r.m.s.d 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.
Rights: NOTICE: This is the author's version of a work accepted for publication by Elsevier. Masumi Eto, Toshio Kitazawa, Fumiko Matsuzawa, Sei-ichi Aikawa, Jason A. Kirkbride, Noriyoshi Isozumi, Yumi Nishimura, David L. Brautigan, Shin-ya Ohki, Structure, 15(12), 2007, 1591-1602, http://dx.doi.org/10.1016/j.str.2007.10.014
URI: http://hdl.handle.net/10119/7870
Material Type: author
Appears in Collections:g10-1. 雑誌掲載論文 (Journal Articles)

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