PubMed:10724160 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/10724160","sourcedb":"PubMed","sourceid":"10724160","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/10724160","text":"Autoinhibition and activation mechanisms of the Wiskott-Aldrich syndrome protein.\nThe Rho-family GTPase, Cdc42, can regulate the actin cytoskeleton through activation of Wiskott-Aldrich syndrome protein (WASP) family members. Activation relieves an autoinhibitory contact between the GTPase-binding domain and the carboxy-terminal region of WASP proteins. Here we report the autoinhibited structure of the GTPase-binding domain of WASP, which can be induced by the C-terminal region or by organic co-solvents. In the autoinhibited complex, intramolecular interactions with the GTPase-binding domain occlude residues of the C terminus that regulate the Arp2/3 actin-nucleating complex. Binding of Cdc42 to the GTPase-binding domain causes a dramatic conformational change, resulting in disruption of the hydrophobic core and release of the C terminus, enabling its interaction with the actin regulatory machinery. These data show that 'intrinsically unstructured' peptides such as the GTPase-binding domain of WASP can be induced into distinct structural and functional states depending on context.","tracks":[{"project":"NCBIDiseaseCorpus","denotations":[{"id":"T1","span":{"begin":48,"end":72},"obj":"Modifier:D014923"},{"id":"T2","span":{"begin":170,"end":194},"obj":"Modifier:D014923"}],"attributes":[{"subj":"T1","pred":"source","obj":"NCBIDiseaseCorpus"},{"subj":"T2","pred":"source","obj":"NCBIDiseaseCorpus"}]},{"project":"NCBI-Disease-Train","denotations":[{"id":"T4293","span":{"begin":48,"end":72},"obj":"Modifier"},{"id":"T4294","span":{"begin":170,"end":194},"obj":"Modifier"}],"attributes":[{"id":"A4293","pred":"database_id","subj":"T4293","obj":"D014923"},{"id":"A4294","pred":"database_id","subj":"T4294","obj":"D014923"},{"subj":"T4293","pred":"source","obj":"NCBI-Disease-Train"},{"subj":"T4294","pred":"source","obj":"NCBI-Disease-Train"}]},{"project":"NCBI-Disease-Corpus-All","denotations":[{"id":"T4293","span":{"begin":48,"end":72},"obj":"Modifier"},{"id":"T4294","span":{"begin":170,"end":194},"obj":"Modifier"}],"attributes":[{"id":"A4293","pred":"database_id","subj":"T4293","obj":"D014923"},{"id":"A4294","pred":"database_id","subj":"T4294","obj":"D014923"},{"subj":"T4293","pred":"source","obj":"NCBI-Disease-Corpus-All"},{"subj":"T4294","pred":"source","obj":"NCBI-Disease-Corpus-All"}]},{"project":"NCBI-Disease-Corpus-2stage-All","denotations":[{"id":"T1","span":{"begin":48,"end":72},"obj":"Modifier"},{"id":"T2","span":{"begin":170,"end":194},"obj":"Modifier"}],"attributes":[{"subj":"T1","pred":"source","obj":"NCBI-Disease-Corpus-2stage-All"},{"subj":"T2","pred":"source","obj":"NCBI-Disease-Corpus-2stage-All"}]},{"project":"NCBI-Disease-Corpus-rezarta-All","denotations":[{"id":"T1","span":{"begin":48,"end":72},"obj":"Modifier"},{"id":"T2","span":{"begin":170,"end":194},"obj":"Modifier"}],"attributes":[{"subj":"T1","pred":"source","obj":"NCBI-Disease-Corpus-rezarta-All"},{"subj":"T2","pred":"source","obj":"NCBI-Disease-Corpus-rezarta-All"}]},{"project":"NCBI-Disease-Corpus-4oGuideline-All","denotations":[{"id":"T1","span":{"begin":48,"end":72},"obj":"SpecificDisease"},{"id":"T2","span":{"begin":170,"end":202},"obj":"SpecificDisease"}],"attributes":[{"subj":"T1","pred":"source","obj":"NCBI-Disease-Corpus-4oGuideline-All"},{"subj":"T2","pred":"source","obj":"NCBI-Disease-Corpus-4oGuideline-All"}]},{"project":"NCBI-Disease-Corpus-Simple-All","denotations":[{"id":"T1","span":{"begin":48,"end":72},"obj":"SpecificDisease"},{"id":"T2","span":{"begin":170,"end":194},"obj":"SpecificDisease"}],"attributes":[{"subj":"T1","pred":"source","obj":"NCBI-Disease-Corpus-Simple-All"},{"subj":"T2","pred":"source","obj":"NCBI-Disease-Corpus-Simple-All"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"NCBIDiseaseCorpus","color":"#93ecd4","default":true},{"id":"NCBI-Disease-Train","color":"#ecba93"},{"id":"NCBI-Disease-Corpus-All","color":"#a093ec"},{"id":"NCBI-Disease-Corpus-2stage-All","color":"#9fec93"},{"id":"NCBI-Disease-Corpus-rezarta-All","color":"#ec93b9"},{"id":"NCBI-Disease-Corpus-4oGuideline-All","color":"#93d3ec"},{"id":"NCBI-Disease-Corpus-Simple-All","color":"#ecea93"}]}]}}