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http://purl.uniprot.org/citations/22577140http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22577140http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22577140http://www.w3.org/2000/01/rdf-schema#comment"Cerebral cavernous malformations (CCMs) affect 0.1-0.5% of the population resulting in leaky vasculature and severe neurological defects. KRIT1 (Krev interaction trapped-1) mutations associate with ∼40% of familial CCMs. KRIT1 is an effector of Ras-related protein 1 (Rap1) GTPase. Rap1 relocalizes KRIT1 from microtubules to cell membranes to impact integrin activation, potentially important for CCM pathology. We report the 1.95 Å co-crystal structure of KRIT1 FERM domain in complex with Rap1. Rap1-KRIT1 interaction encompasses an extended surface, including Rap1 Switch I and II and KRIT1 FERM F1 and F2 lobes. Rap1 binds KRIT1-F1 lobe using a GTPase-ubiquitin-like fold interaction but binds KRIT1-F2 lobe by a novel interaction. Point mutagenesis confirms the interaction. High similarity between KRIT1-F2/F3 and talin is revealed. Additionally, the mechanism for FERM domains acting as GTPase effectors is suggested. Finally, structure-based alignment of each lobe suggests classification of FERM domains as ERM-like and TMFK-like (talin-myosin-FAK-KRIT-like) and that FERM lobes resemble domain "modules.""xsd:string
http://purl.uniprot.org/citations/22577140http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m112.361295"xsd:string
http://purl.uniprot.org/citations/22577140http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m112.361295"xsd:string
http://purl.uniprot.org/citations/22577140http://purl.uniprot.org/core/author"Li X."xsd:string
http://purl.uniprot.org/citations/22577140http://purl.uniprot.org/core/author"Li X."xsd:string
http://purl.uniprot.org/citations/22577140http://purl.uniprot.org/core/author"Liu W."xsd:string
http://purl.uniprot.org/citations/22577140http://purl.uniprot.org/core/author"Liu W."xsd:string
http://purl.uniprot.org/citations/22577140http://purl.uniprot.org/core/author"Zhang R."xsd:string
http://purl.uniprot.org/citations/22577140http://purl.uniprot.org/core/author"Zhang R."xsd:string
http://purl.uniprot.org/citations/22577140http://purl.uniprot.org/core/author"Calderwood D.A."xsd:string
http://purl.uniprot.org/citations/22577140http://purl.uniprot.org/core/author"Calderwood D.A."xsd:string
http://purl.uniprot.org/citations/22577140http://purl.uniprot.org/core/author"Boggon T.J."xsd:string
http://purl.uniprot.org/citations/22577140http://purl.uniprot.org/core/author"Boggon T.J."xsd:string
http://purl.uniprot.org/citations/22577140http://purl.uniprot.org/core/author"Draheim K.M."xsd:string
http://purl.uniprot.org/citations/22577140http://purl.uniprot.org/core/author"Draheim K.M."xsd:string
http://purl.uniprot.org/citations/22577140http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22577140http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22577140http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/22577140http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/22577140http://purl.uniprot.org/core/pages"22317-22327"xsd:string
http://purl.uniprot.org/citations/22577140http://purl.uniprot.org/core/pages"22317-22327"xsd:string
http://purl.uniprot.org/citations/22577140http://purl.uniprot.org/core/title"Structural basis for small G protein effector interaction of Ras-related protein 1 (Rap1) and adaptor protein Krev interaction trapped 1 (KRIT1)."xsd:string
http://purl.uniprot.org/citations/22577140http://purl.uniprot.org/core/title"Structural basis for small G protein effector interaction of Ras-related protein 1 (Rap1) and adaptor protein Krev interaction trapped 1 (KRIT1)."xsd:string