title: Remarkably fast coupled folding and binding of the intrinsically disordered transactivation domain of cMyb to CBP KIX.
abstract: Association rates for interactions between folded proteins have been investigated extensively, allowing the development of computational and theoretical prediction methods. Less is known about association rates for complexes where one or more partner is initially disordered, despite much speculation about how they may compare to those for folded proteins. We have attached a fluorophore to the N-terminus of the 25 amino acid cMyb peptide used previously in NMR and equilibrium studies (termed FITC-cMyb), and used this to monitor the kinetics of its interaction with the KIX protein. We have investigated the ionic strength and temperature dependence of the kinetics, and conclude that the association process is extremely fast, apparently exceeding the rates predicted by formulations applicable to interactions between pairs of folded proteins. This is despite the fact that not all collisions result in complex formation (there is an observable activation energy for the association process). We propose that this is partially a result of the disordered nature of the FITC-cMyb peptide itself.
authors.affiliation: Department of Chemistry, University of Cambridge , Lensfield Road, Cambridge, CB2 1EW, U.K.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Shammas
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Travis
authors.forename: Jane
authors.initials: J
authors.lastname: Clarke
mesh_terms: D000818:Animals; D002942:Circular Dichroism; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D007700:Kinetics; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009994:Osmolar Concentration; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D020598:Proto-Oncogene Proteins c-myb / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics
chemical_list: D008565:Membrane Proteins; C498709:Pag1 protein, mouse; D010455:Peptides; D010750:Phosphoproteins; D020598:Proto-Oncogene Proteins c-myb; D011994:Recombinant Proteins; D016650:Fluorescein-5-isothiocyanate