Document Detail


Crystal structure of MO25 alpha in complex with the C terminus of the pseudo kinase STE20-related adaptor.
MedLine Citation:
PMID:  14730349     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Christine C Milburn; Jérôme Boudeau; Maria Deak; Dario R Alessi; Daan M F van Aalten
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-01-18
Journal Detail:
Title:  Nature structural & molecular biology     Volume:  11     ISSN:  1545-9993     ISO Abbreviation:  Nat. Struct. Mol. Biol.     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-01-29     Completed Date:  2004-04-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  101186374     Medline TA:  Nat Struct Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  193-200     Citation Subset:  IM    
Affiliation:
Division of Biological Chemistry & Molecular Microbiology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland.
Data Bank Information
Bank Name/Acc. No.:
PDB/1UPK;  1UPL
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing*
Adaptor Proteins, Vesicular Transport / genetics,  metabolism*
Amino Acid Sequence
Animals
Base Sequence
Carrier Proteins / chemistry*,  metabolism
Crystallography, X-Ray
DNA Primers
Mice
Models, Molecular
Molecular Sequence Data
Mutagenesis
Protein Binding
Protein Conformation
Sequence Homology, Amino Acid
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Adaptor Proteins, Vesicular Transport; 0/Carrier Proteins; 0/DNA Primers; 0/MO25alpha protein, mouse; 0/STRAD protein, human

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