Structural insight into dimeric interaction of the SARAH domains from Mst1 and RASSF family proteins in the apoptosis pathway.

In eukaryotic cells, apoptosis and cell cycle arrest by the Ras --> RASSF --> MST pathway are controlled by the interaction of (for Salvador/Rassf/Hippo) domains in the C-terminal part of tumor suppressor proteins. The Mst1 duanyu1800H 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 duanyu1800H domain and its heterotypic interaction with the Rassf5 and Salvador (Sav) duanyu1800H domain. The Mst1 duanyu1800H structure forms a homodimer containing two helices per monomer. An antiparallel arrangement of the long alpha-helices (h2/h2') provides an elongated binding interface between the two monomers, and the short 3(10) helices (h1/h1') are folded toward that of the other monomer. Chemical shift perturbation experiments identified an elongated, tight-binding interface with the Rassf5 duanyu1800H domain and a 1:1 heterodimer formation. The linker region between the kinase and the duanyu1800H 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 duanyu1800H domain.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}