Structural basis of the heterodimerization of the MST and RASSF SARAH domains in the Hippo signalling pathway
- Authors
- Hwang, Eunha; Cheong, Hae-Kap; Ul Mushtaq, Ameeq; Kim, Hye-Yeon; Yeo, Kwon Joo; Kim, Eunhee; Lee, Woo Cheol; Hwang, Kwang Yeon; Cheong, Chaejoon; Jeon, Young Ho
- Issue Date
- 7월-2014
- Publisher
- INT UNION CRYSTALLOGRAPHY
- Keywords
- Hippo signalling pathway; MST; RASSF; SARAH domains
- Citation
- ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, v.70, pp.1944 - 1953
- Indexed
- SCIE
SCOPUS
- Journal Title
- ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
- Volume
- 70
- Start Page
- 1944
- End Page
- 1953
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/98016
- DOI
- 10.1107/S139900471400947X
- ISSN
- 2059-7983
- Abstract
- Despite recent progress in research on the Hippo signalling pathway, the structural information available in this area is extremely limited. Intriguingly, the homodimeric and heterodimeric interactions of mammalian sterile 20-like (MST) kinases through the so-called 'SARAH' (SAV/RASSF/HPO) domains play a critical role in cellular homeostasis, dictating the fate of the cell regarding cell proliferation or apoptosis. To understand the mechanism of the heterodimerization of SARAH domains, the three-dimensional structures of an MST1-RASSF5 SARAH heterodimer and an MST2 SARAH homodimer were determined by X-ray crystallography and were analysed together with that previously determined for the MST1 SARAH homodimer. While the structure of the MST2 homodimer resembled that of the MST1 homodimer, the MST1-RASSF5 heterodimer showed distinct structural features. Firstly, the six N-terminal residues (Asp432-Lys437), which correspond to the short N-terminal 310-helix h1 kinked from the h2 helix in the MST1 homodimer, were disordered. Furthermore, the MST1 SARAH domain in the MST1-RASSF5 complex showed a longer helical structure (Ser438-Lys480) than that in the MST1 homodimer (Val441-Lys480). Moreover, extensive polar and nonpolar contacts in the MST1-RASSF5 SARAH domain were identified which strengthen the interactions in the heterodimer in comparison to the interactions in the homodimer. Denaturation experiments performed using urea also indicated that the MST-RASSF heterodimers are substantially more stable than the MST homodimers. These findings provide structural insights into the role of the MST1-RASSF5 SARAH domain in apoptosis signalling.
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