Insights into Coupled Folding and Binding Mechanisms from Kinetic Studies

• Published in: The Journal of biological chemistry Vol. 291; no. 13; pp. 6689 - 6695
• Main Authors: Shammas, Sarah L., Crabtree, Michael D., Dahal, Liza, Wicky, Basile I.M., Clarke, Jane
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.03.2016; American Society for Biochemistry and Molecular Biology
• Subjects: Apoptosis Regulatory Proteins - chemistry; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; biophysics; coupled folding and binding; CREB-Binding Protein - chemistry; CREB-Binding Protein - genetics; CREB-Binding Protein - metabolism; Cyclic AMP Response Element-Binding Protein - chemistry; Cyclic AMP Response Element-Binding Protein - genetics; Cyclic AMP Response Element-Binding Protein - metabolism; electrostatics; Humans; Hydrophobic and Hydrophilic Interactions; IDP; Intrinsically Disordered Proteins - chemistry; Intrinsically Disordered Proteins - genetics; Intrinsically Disordered Proteins - metabolism; Kinetics; Minireviews; Molecular Dynamics Simulation; Myeloid Cell Leukemia Sequence 1 Protein - chemistry; Myeloid Cell Leukemia Sequence 1 Protein - genetics; Myeloid Cell Leukemia Sequence 1 Protein - metabolism; phi-value; Protein Binding; protein dynamic; protein electrostatics; Protein Folding; Protein Interaction Domains and Motifs; protein-protein interactions; Proto-Oncogene Proteins - chemistry; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; residual structure; Signal Transduction; signaling; Static Electricity; Thermodynamics; signaling; residual structure; electrostatics; IDP; coupled folding and binding; protein electrostatics; protein folding; phi-value; kinetics; biophysics; protein dynamic; protein-protein interactions
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.R115.692715

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.