title: Promiscuity in protein-RNA interactions: conformational ensembles facilitate molecular recognition in the spliceosome: conformational diversity in U2AF⁶⁵ facilitates binding to diverse RNA sequences.
abstract: Here I discuss findings that suggest a universal mechanism for proteins (and RNA) to recognize and interact with various binding partners by selectively binding to different conformations that pre-exist in the free protein's conformational ensemble. The tandem RNA recognition motif domains of splicing factor U2AF⁶⁵ fluctuate in solution between a predominately closed conformation in which the RNA binding site of one of the domains is blocked, and a lowly populated open conformation in which both RNA binding pockets are accessible. RNA binding to U2AF⁶⁵ may thus occur through the weakly populated open conformation, and the binding interaction stabilizes the open conformation. The conformational diversity observed in U2AF⁶⁵ might also facilitate binding to diverse RNA sequences as found in the polypyrimidine tracts that help define 3' splice sites. Similar binding pathways in other systems have important consequences in biological regulation, molecular evolution, and information storage.
authors.affiliation: Department of Chemistry, The Pennsylvania State University, 240 Chemistry Building, University Park, PA, USA. ddb12@psu.edu
authors.forename: David D
authors.initials: DD
authors.lastname: Boehr
mesh_terms: D020816:Amino Acid Motifs; D001483:Base Sequence; D055162:Biocatalysis; D019143:Evolution, Molecular; D014644:Genetic Variation; D046911:Macromolecular Substances / Q000737:chemistry; D009687:Nuclear Proteins / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D011110:Polymorphism, Genetic; D011485:Protein Binding; D011487:Protein Conformation; D022821:RNA Splice Sites; D012326:RNA Splicing; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D012261:Ribonucleoproteins / Q000737:chemistry*; D017381:Spliceosomes / Q000737:chemistry* / Q000235:genetics; D000072668:Splicing Factor U2AF
chemical_list: D046911:Macromolecular Substances; D009687:Nuclear Proteins; D022821:RNA Splice Sites; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D000072668:Splicing Factor U2AF