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

Nat Struct Mol Biol. 2004 Feb;11(2):193-200. doi: 10.1038/nsmb716. Epub 2004 Jan 18.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Adaptor Proteins, Vesicular Transport / genetics
  • Adaptor Proteins, Vesicular Transport / metabolism*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Calcium-Binding Proteins
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism
  • Crystallography, X-Ray
  • DNA Primers
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis
  • Protein Binding
  • Protein Conformation
  • Sequence Homology, Amino Acid


  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • Cab39 protein, mouse
  • Calcium-Binding Proteins
  • Carrier Proteins
  • DNA Primers
  • STRADA protein, human

Associated data

  • PDB/1UPK
  • PDB/1UPL