1UPK

Crystal structure of MO25 in complex with a C-terminal peptide of STRAD

Summary for 1UPK

• Entry DOI: 10.2210/pdb1upk/pdb
• Related: 1UPL
• Descriptor: MO25 PROTEIN, STE-20 RELATED ADAPTOR, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (4 entities in total)
• Functional Keywords: transferase, mo25, strad, ste-20 related adaptor, armadillo
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 2
• Total formula weight: 42077.80

Authors

Milburn, C.C.,Boudeau, J.,Deak, M.,Alessi, D.R.,Van Aalten, D.M.F. (deposition date: 2003-10-07, release date: 2004-01-22, Last modification date: 2024-10-16)

Primary citation

Milburn, C.C.,Boudeau, J.,Deak, M.,Alessi, D.R.,Van Aalten, D.M.F.
Crystal Structure of Mo25 Alpha in Complex with the C-Terminus of the Pseudo Kinase Ste-20 Related Adaptor (Strad)
Nat.Struct.Mol.Biol., 11:193-, 2004

PubMed 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.

PubMed: 14730349
DOI: 10.1038/NSMB716

Experimental method

X-RAY DIFFRACTION (1.85 Å)