title: Insights into Coupled Folding and Binding Mechanisms from Kinetic Studies.
abstract: Intrinsically disordered proteins (IDPs) are characterized by a lack of persistent structure. Since their identification more than a decade ago, many questions regarding their functional relevance and interaction mechanisms remain unanswered. Although most experiments have taken equilibrium and structural perspectives, fewer studies have investigated the kinetics of their interactions. Here we review and highlight the type of information that can be gained from kinetic studies. In particular, we show how kinetic studies of coupled folding and binding reactions, an important class of signaling event, are needed to determine mechanisms.
authors: From the Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom sls42@cam.ac.uk.
authors: Sarah L
authors: http://orcid.org/0000-0003-4489-140X
authors: SL
authors: Shammas
authors: From the Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom.
authors: Michael D
authors: MD
authors: Crabtree
authors: From the Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom.
authors: Liza
authors: L
authors: Dahal
authors: From the Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom.
authors: Basile I M
authors: BI
authors: Wicky
authors: From the Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom jc162@cam.ac.uk.
authors: Jane
authors: J
authors: Clarke
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D050882:CREB-Binding Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D064267:Intrinsically Disordered Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D064267:Intrinsically Disordered Proteins; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D011518:Proto-Oncogene Proteins; D050882:CREB-Binding Protein; C494363:CREBBP protein, human
keywords: IDP; biophysics; coupled folding and binding; electrostatics; kinetics; phi-value; protein dynamic; protein electrostatics; protein folding; protein-protein interactions; residual structure; signaling