title: Large-scale movement of functional domains facilitates aminoacylation by human mitochondrial phenylalanyl-tRNA synthetase.
abstract: Structural studies suggest rearrangement of the RNA-binding and catalytic domains of human mitochondrial PheRS (mtPheRS) is required for aminoacylation. Crosslinking the catalytic and RNA-binding domains resulted in a "closed" form of mtPheRS that still catalyzed ATP-dependent Phe activation, but was no longer able to transfer Phe to tRNA and complete the aminoacylation reaction. SAXS experiments indicated the presence of both the closed and open forms of mtPheRS in solution. Together, these results indicate that conformational flexibility of the two functional modules in mtPheRS is essential for its phenylalanylation activity. This is consistent with the evolution of the aminoacyl-tRNA synthetases as modular enzymes consisting of separate domains that display independent activities.
authors.affiliation: Department of Microbiology and Center for RNA Biology, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Srujana S
authors.initials: SS
authors.lastname: Yadavalli
authors.forename: Liron
authors.initials: L
authors.lastname: Klipcan
authors.forename: Alexey
authors.initials: A
authors.lastname: Zozulya
authors.forename: Rajat
authors.initials: R
authors.lastname: Banerjee
authors.forename: Dmitri
authors.initials: D
authors.lastname: Svergun
authors.forename: Mark
authors.initials: M
authors.lastname: Safro
authors.forename: Michael
authors.initials: M
authors.lastname: Ibba
mesh_terms: D002384:Catalysis; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D006801:Humans; D008928:Mitochondria / Q000201:enzymology*; D008956:Models, Chemical; D010649:Phenylalanine / Q000378:metabolism*; D010652:Phenylalanine-tRNA Ligase / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012343:RNA, Transfer / Q000378:metabolism*; D053838:Scattering, Small Angle; D046249:Transfer RNA Aminoacylation
chemical_list: D010649:Phenylalanine; D012343:RNA, Transfer; D010652:Phenylalanine-tRNA Ligase