| Crystal structure of MO25 alpha in complex with the C terminus of the pseudo kinase STE20-related adaptor. | |
MedLine Citation:
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PMID: 14730349 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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:
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Christine C Milburn; Jérôme Boudeau; Maria Deak; Dario R Alessi; Daan M F van Aalten |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2004-01-18 |
Journal Detail:
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Title: Nature structural & molecular biology Volume: 11 ISSN: 1545-9993 ISO Abbreviation: Nat. Struct. Mol. Biol. Publication Date: 2004 Feb |
Date Detail:
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Created Date: 2004-01-29 Completed Date: 2004-04-05 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 101186374 Medline TA: Nat Struct Mol Biol Country: United States |
Other Details:
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Languages: eng Pagination: 193-200 Citation Subset: IM |
Affiliation:
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Division of Biological Chemistry & Molecular Microbiology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland. |
| Data Bank Information | |
Bank Name/Acc. No.:
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PDB/1UPK; 1UPL |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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