Large-scale movement of functional domains facilitates aminoacylation by human mitochondrial phenylalanyl-tRNA synthetase.
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.
Yadavalli
Srujana S
SS
Department of Microbiology and Center for RNA Biology, Ohio State University, Columbus, OH 43210, USA.
Klipcan
Liron
L
Zozulya
Alexey
A
Banerjee
Rajat
R
Svergun
Dmitri
D
Safro
Mark
M
Ibba
Michael
M
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
D010649:Phenylalanine; D012343:RNA, Transfer; D010652:Phenylalanine-tRNA Ligase