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http://hdl.handle.net/10119/7870
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| 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: | f10-1. 雑誌掲載論文 (Journal Articles)
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