title: Role of dimerization in KH/RNA complexes: the example of Nova KH3.
abstract: The K homology module, one of the most common RNA-binding motifs, is present in multiple copies in both prokaryotic and eukaryotic regulatory proteins. Increasing evidence suggests that self-aggregation of KH modules has a functional role. We have used a combination of techniques to characterize the behavior in solution of the third KH domain of Nova-1, a paradigmatic KH protein. The possibility of working on the isolated module allowed us to observe specifically the homodimerization and RNA-binding properties of KH domains. We provide conclusive evidence that self-association of Nova-1 KH3 occurs in solution even in the absence of RNA. Homodimerization involves a specific protein/protein interface. We also studied the dynamical behavior of Nova-1 KH3 in isolation and in complex with RNA. These data provide a model for the mechanism of KH/RNA recognition and suggest functional implications of dimerization in KH complexes. We discuss our findings in the context of the whole KH family and suggest a generalized mode of interaction.
authors.affiliation: NIMR, The Ridgeway, London NW7 1AA, United Kingdom.
authors.forename: Andres
authors.initials: A
authors.lastname: Ramos
authors.forename: David
authors.initials: D
authors.lastname: Hollingworth
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Major
authors.forename: Salvatore
authors.initials: S
authors.lastname: Adinolfi
authors.forename: Geoff
authors.initials: G
authors.lastname: Kelly
authors.forename: Fred W
authors.initials: FW
authors.lastname: Muskett
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pastore
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm; D001483:Base Sequence; D019281:Dimerization; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008957:Models, Genetic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D000090682:Neuro-Oncological Ventral Antigen; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry*; D012261:Ribonucleoproteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D014461:Ultracentrifugation
chemical_list: D000951:Antigens, Neoplasm; D009419:Nerve Tissue Proteins; D000090682:Neuro-Oncological Ventral Antigen; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D012313:RNA