한빛사 논문
Abstract
( tumor suppressor | cell cycle arrest | Hippo | Salvador )
Eunha Hwang *, Kyoung-Seok Ryu *, Kimmo Pääkkönen , Peter Güntert , Hae-Kap Cheong *, Dae-Sik Lim , Jie-Oh Lee , Young Ho Jeon *¶, and Chaejoon Cheong *¶
*Magnetic Resonance Team, Korea Basic Science Institute, 804-1 Yangchung-Ri, Ochang, Chungbuk 363-883, Korea; Tatsuo Miyazawa Memorial Program, RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045, Japan; Departments of Biological Sciences and Chemistry, Korea Advanced Institute of Science and Technology, 373-1 Guseoung-D, Yuseong-G, Daejeon 305-701, Korea
Edited by Alfred G. Redfield, Brandeis University, Waltham, MA, and approved April 16, 2007 (received for review December 5, 2006)
In eukaryotic cells, apoptosis and cell cycle arrest by the Ras RASSF MST pathway are controlled by the interaction of SARAH (for Salvador/Rassf/Hippo) domains in the C-terminal part of tumor suppressor proteins. The Mst1 SARAH domain interacts with its homologous domain of Rassf1 and Rassf5 (also known as Nore1) by forming a heterodimer that mediates the apoptosis process. Here, we describe the homodimeric structure of the human Mst1 SARAH domain and its heterotypic interaction with the Rassf5 and Salvador (Sav) SARAH domain. The Mst1 SARAH structure forms a homodimer containing two helices per monomer. An antiparallel arrangement of the long -helices (h2/h2'') provides an elongated binding interface between the two monomers, and the short 310 helices (h1/h1'') are folded toward that of the other monomer. Chemical shift perturbation experiments identified an elongated, tight-binding interface with the Rassf5 SARAH domain and a 1:1 heterodimer formation. The linker region between the kinase and the SARAH domain is shown to be disordered in the free protein. These results imply a novel mode of interaction with RASSF family proteins and provide insight into the mechanism of apoptosis control by the SARAH domain.
Author contributions: Y.H.J. and C.C. designed research; E.H., K.-S.R., and Y.H.J. performed research; H.-K.C. and D.-S.L. contributed new reagents/analytic tools; K.-S.R., K.P., P.G., and J.-O.L. analyzed data; and P.G., Y.H.J., and C.C. wrote the paper.
The authors declare no conflict of interest.
¶To whom correspondence may be addressed.
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