title: Mutational Analysis of the Binding-Induced Folding Reaction of the Mixed-Lineage Leukemia Protein to the KIX Domain.
abstract: Intrinsically disordered proteins represent a large class of proteins that lack a well-defined three-dimensional structure in isolation but can undergo a disorder to order transition upon binding to their physiological ligands. Understanding the mechanism by which these proteins fold upon binding represents a challenge. Here we present a detailed mutational study of the kinetics of the binding reaction between the transactivation domain of the mixed-lineage leukemia protein, an intrinsically disordered protein, and the KIX domain, performed under different experimental conditions. The experimental data allow us to infer the mechanism of folding upon binding and to pinpoint the key interactions present in the transition state. Furthermore, we identify a peculiar malleability of the observed mechanism upon changes in reaction conditions. This finding, which is in opposition to the robustness typically observed in the folding of globular proteins, is discussed in the context of previous work on intrinsically disordered proteins.
authors.affiliation: Istituto Pasteur Fondazione Cenci Bolognetti and Istituto di Biologia e Patologia Molecolari del CNR, Dipartimento di Scienze Biochimiche "A. Rossi Fanelli", Sapienza Università di Roma , P. le A. Moro 5, 00185 Rome, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Toto
authors.affiliation: Istituto Pasteur Fondazione Cenci Bolognetti and Istituto di Biologia e Patologia Molecolari del CNR, Dipartimento di Scienze Biochimiche "A. Rossi Fanelli", Sapienza Università di Roma , P. le A. Moro 5, 00185 Rome, Italy.|Department of Chemistry, University of Cambridge , Lensfield Road, Cambridge CB2 1EW, United Kingdom.
authors.forename: Stefano
authors.initials: S
authors.lastname: Gianni
mesh_terms: D000595:Amino Acid Sequence; D004252:DNA Mutational Analysis; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D051788:Myeloid-Lymphoid Leukemia Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D000072417:Protein Domains; D017510:Protein Folding
chemical_list: D051788:Myeloid-Lymphoid Leukemia Protein