Parallel Coiled-coil Association of the RhoA-binding Domain in Rho-kinase

Toshiyuki Shimizu, Kentaro Ihara, Ryoko Maesaki, Mutsuki Amano, Kozo Kaibuchi, Toshio Hakoshima

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)

Abstract

Rho-kinase is a serine/threonine protein kinase that regulates cytoskeletal events in cells. The enzyme activity of Rho-kinase is auto-inhibited in the free state but is activated through direct binding to the small GTPase Rho in the GTP-bound form. The crystal structure of the Rho-binding domain (RhoBD) of Rho-kinase has been determined at 1.8-Å resolution by the multi-wavelength anomalous dispersion technique. The structure shows that RhoBD dimerizes to form a parallel coiled-coil with long consecutive α-helices extended to ∼97 Å and suggests that free Rho-kinase can also form a dimer through parallel self-association. At the middle region of the coiled-coil, the polypeptide chains are flexible and display loose "knobs-into-holes" packing of the side chains from both chains. RhoBD residues that have been shown to be critical for Rho-binding are spread in the positively charged C-terminal region. The parallel coiled-coil structure of our Rho-kinase RhoBD in the free form is different from the anti-parallel coiled-coil structure of RhoBD of protein kinase N when complexed with RhoA. Implications derived from these structural studies in relation to the mechanism of Rho-kinase activation will be addressed with previously reported experimental data.

Original languageEnglish
Pages (from-to)46046-46051
Number of pages6
JournalJournal of Biological Chemistry
Volume278
Issue number46
DOIs
Publication statusPublished - 14-11-2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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