2JO8

Solution structure of C-terminal domain of human mammalian sterile 20-like kinase 1 (MST1)

Summary for 2JO8

• Entry DOI: 10.2210/pdb2jo8/pdb
• Descriptor: Serine/threonine-protein kinase 4 (1 entity in total)
• Functional Keywords: protein, c-terminal domain, human mammalian sterile 20-like kinase 1, dimer, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q13043
• Total number of polymer chains: 2
• Total formula weight: 12239.94

Authors

Hwang, E.,Ryu, K.-S.,Paakkonen, K.,Guntert, P.,Cheong, H.-K.,Lim, D.-S.,Lee, J.O.,Jeon, Y.H.,Cheong, C. (deposition date: 2007-02-26, release date: 2007-05-15, Last modification date: 2023-12-20)

Primary citation

Hwang, E.,Ryu, K.-S.,Paakkonen, K.,Guntert, P.,Cheong, H.-K.,Lim, D.-S.,Lee, J.-O.,Jeon, Y.H.,Cheong, C.
Structural insight into dimeric interaction of the SARAH domains from Mst1 and RASSF family proteins in the apoptosis pathway
Proc.Natl.Acad.Sci.Usa, 104:9236-9241, 2007

PubMed Abstract: 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 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 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.

PubMed: 17517604
DOI: 10.1073/pnas.0610716104

Experimental method

SOLUTION NMR