title: Stochastic machines as a colocalization mechanism for scaffold protein function.
abstract: The axis inhibition (Axin) scaffold protein colocalizes β-catenin, casein kinase Iα, and glycogen synthetase kinase 3β by their binding to Axin's long intrinsically disordered region, thereby yielding structured domains with flexible linkers. This complex leads to the phosphorylation of β-catenin, marking it for destruction. Fusing proteins with flexible linkers vastly accelerates chemical interactions between them by their colocalization. Here we propose that the complex works by random movements of a "stochastic machine," not by coordinated conformational changes. This non-covalent, modular assembly process allows the various molecular machine components to be used in multiple processes.
authors.affiliation: Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Xue
authors.forename: Pedro R
authors.initials: PR
authors.lastname: Romero
authors.forename: Maria
authors.initials: M
authors.lastname: Noutsou
authors.forename: Madelon M
authors.initials: MM
authors.lastname: Maurice
authors.forename: Stefan G D
authors.initials: SG
authors.lastname: Rüdiger
authors.forename: Albert M
authors.initials: AM
authors.lastname: William
authors.forename: Marcin J
authors.initials: MJ
authors.lastname: Mizianty
authors.forename: Lukasz
authors.initials: L
authors.lastname: Kurgan
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Uversky
authors.forename: A Keith
authors.initials: AK
authors.lastname: Dunker
mesh_terms: D000494:Allosteric Regulation; D060465:Axin Signaling Complex / Q000737:chemistry* / Q000502:physiology; D047389:Casein Kinase I / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D020836:Protein Structure, Quaternary; D021381:Protein Transport; D059748:Proteolysis; D013269:Stochastic Processes; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000737:chemistry
chemical_list: D060465:Axin Signaling Complex; D051176:beta Catenin; D047389:Casein Kinase I