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Nat Struct Mol Biol. 2004 Feb;11(2):193-200. Epub 2004 Jan 18.

Crystal structure of MO25 alpha in complex with the C terminus of the pseudo kinase STE20-related adaptor.

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1
Division of Biological Chemistry & Molecular Microbiology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland.

Abstract

Mouse protein 25 alpha (MO25 alpha) is a 40-kDa protein that, together with the STE20-related adaptor-alpha (STRAD alpha) pseudo kinase, forms a regulatory complex capable of stimulating the activity of the LKB1 tumor suppressor protein kinase. The latter is mutated in the inherited Peutz-Jeghers cancer syndrome (PJS). MO25 alpha binds directly to a conserved Trp-Glu-Phe sequence at the STRAD alpha C terminus, markedly enhancing binding of STRAD alpha to LKB1 and increasing LKB1 catalytic activity. The MO25 alpha crystal structure reveals a helical repeat fold, distantly related to the Armadillo proteins. A complex with the STRAD alpha peptide reveals a hydrophobic pocket that is involved in a unique and specific interaction with the Trp-Glu-Phe motif, further supported by mutagenesis studies. The data represent a first step toward structural analysis of the LKB1-STRAD-MO25 complex, and suggests that MO25 alpha is a scaffold protein to which other regions of STRAD-LKB1, cellular LKB1 substrates or regulatory components could bind.

PMID:
14730349
DOI:
10.1038/nsmb716
[Indexed for MEDLINE]
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