title: Identifying intrinsically disordered protein regions likely to undergo binding-induced helical transitions.
abstract: Many proteins contain intrinsically disordered regions (IDRs) lacking stable secondary and ordered tertiary structure. IDRs are often implicated in macromolecular interactions, and may undergo structural transitions upon binding to interaction partners. However, as binding partners of many protein IDRs are unknown, these structural transitions are difficult to verify and often are poorly understood. In this study we describe a method to identify IDRs that are likely to undergo helical transitions upon binding. This method combines bioinformatics analyses followed by circular dichroism spectroscopy to monitor 2,2,2-trifluoroethanol (TFE)-induced changes in secondary structure content of these IDRs. Our results demonstrate that there is no significant change in the helicity of IDRs that are not predicted to fold upon binding. IDRs that are predicted to fold fall into two groups: one group does not become helical in the presence of TFE and includes examples of IDRs that form β-strands upon binding, while the other group becomes more helical and includes examples that are known to fold into helices upon binding. Therefore, we propose that bioinformatics analyses combined with experimental evaluation using TFE may provide a general method to identify IDRs that undergo binding-induced disorder-to-helix transitions.
authors.affiliation: Department of Chemistry and Biochemistry, North Dakota State University, Fargo, ND 58108-6050, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Glover
authors.affiliation: Department of Chemistry and Biochemistry, North Dakota State University, Fargo, ND 58108-6050, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Mei
authors.affiliation: Department of Chemistry and Biochemistry, North Dakota State University, Fargo, ND 58108-6050, USA. Electronic address: Sangita.Sinha@ndsu.edu.
authors.forename: Sangita C
authors.initials: SC
authors.lastname: Sinha
mesh_terms: D002942:Circular Dichroism / Q000379:methods; D019295:Computational Biology / Q000379:methods; D064267:Intrinsically Disordered Proteins / Q000737:chemistry*; D011485:Protein Binding / Q000502:physiology; D000072417:Protein Domains / Q000502:physiology; D017433:Protein Structure, Secondary; D014270:Trifluoroethanol / Q000737:chemistry
chemical_list: D064267:Intrinsically Disordered Proteins; D014270:Trifluoroethanol
keywords: 2,2,2-Trifluoroethanol; Anchor region; Circular dichroism; Disorder-to-helix transition; Intrinsically disordered region; Protein-protein interaction