Large-scale movement of functional domains facilitates aminoacylation by human mitochondrial phenylalanyl-tRNA synthetase

TY - JOUR

T1 - Large-scale movement of functional domains facilitates aminoacylation by human mitochondrial phenylalanyl-tRNA synthetase

AU - Yadavalli, Srujana S.

AU - Klipcan, Liron

AU - Zozulya, Alexey

AU - Banerjee, Rajat

AU - Svergun, Dmitri

AU - Safro, Mark

AU - Ibba, Michael

N1 - Funding Information: We thank H. Roy and T. Rogers for critical reading of the manuscript. This work was supported by grants from the Binational Science Foundation (2005209, MS and MI), National Science Foundation (744791, MI), and the EU Design Study SAXIER (011934, AVZ and DIS). LK is grateful to the Ori Foundation for a doctoral research fellowship.

PY - 2009/10/6

Y1 - 2009/10/6

N2 - 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.

AB - 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.

KW - Aminoacylation

KW - Mitochondrion

KW - Protein synthesis

KW - Translation

KW - tRNA

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U2 - 10.1016/j.febslet.2009.09.008

DO - 10.1016/j.febslet.2009.09.008

M3 - Article

C2 - 19737557

SN - 0014-5793

VL - 583

SP - 3204

EP - 3208

JO - FEBS Letters

JF - FEBS Letters

IS - 19

ER -