title: Actin-Induced Structure in the Beta-Thymosin Family of Intrinsically Disordered Proteins.
abstract: Thymosin β4 (Tβ4) is a 43-amino acid signature motif peptide that defines the beta-thymosin (βT) family of proteins. βTs are intrinsically unstructured in their free states and undergo disorder-to-order transitions in carrying out their biological functions. This property poses challenges in determining their 3D structures, mainly favoring structural studies on the complexes formed between βTs and their interaction partners. One of the βTs' primary binding partners is monomeric actin, a major component of the cytoskeleton in eukaryotic cells. Tβ4's role in this system is to maintain the highly concentrated pool of monomeric actin that can be accessed through profilin by actin filament nucleating machineries. Here, we give an account of the structures of βTs that have been illuminated by nuclear magnetic resonance (NMR) and X-ray crystallography. NMR has been the method of choice for probing regions that have intrinsic conformational preference within the largely disordered βTs in their native states in solution. X-ray crystallography has demonstrated at atomic detail how βTs interact with actin. Detailed analysis of these structures highlights the disorder-to-order transition of Tβ4 in binding to actin and its isoform specificity.
authors.affiliation: Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), Biopolis, Singapore. Electronic address: bxue@imcb.a-star.edu.sg.
authors.forename: B
authors.initials: B
authors.lastname: Xue
authors.affiliation: Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), Biopolis, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore; NTU Institute of Structural Biology, Nanyang Technological University, Singapore; School of Biological Sciences, Nanyang Technological University, Singapore; Lee Kong Chan School of Medicine, Singapore.
authors.forename: R C
authors.initials: RC
authors.lastname: Robinson
mesh_terms: D000199:Actins / Q000378:metabolism / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D006801:Humans; D064267:Intrinsically Disordered Proteins / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D012996:Solutions; D012997:Solvents; D013947:Thymosin / Q000737:chemistry* / Q000378:metabolism; D014867:Water; D000099201:Thymosin beta(4)
chemical_list: D000199:Actins; D064267:Intrinsically Disordered Proteins; D012996:Solutions; D012997:Solvents; D013947:Thymosin; D014867:Water; D000099201:Thymosin beta(4); C039302:thymosin beta(10)
keywords: Actin; Beta-thymosin; Crystallography; Intrinsically disordered/unstructured proteins; NMR; Protein hybrid; Structure; Thymosin β4