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Molecular trigger for pre-transfer editing pathway in Valyl-tRNA synthetase: A molecular dynamics simulation study

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Abstract

Pre-transfer editing pathway in Valyl-tRNA synthetase (ValRS) is a very important process to maintain the high fidelity of protein synthesis. However, molecular basis for this pathway remains unclear. Here we employed molecular dynamics (MD) simulation to study two complexes, ValRS·tRNAval·Val-AMP (complex V) and ValRS·tRNAval·Thr-AMP (complex T), and compared their simulation trajectories, in order to understand how the pre-transfer editing pathway is triggered by the noncognate substrate Thr-AMP. The MD simulations showed that the binding of Thr-AMP to ValRS led to different motions from those in complex V: clockwise rotation of the editing domain along the hinge region, and strong motions in the catalytic domain, especially in KMSKS loop. We found that the changed motion of Trp495 induced by Thr-AMP serves as a signal to discriminate Thr-AMP from Val-AMP, and the rigid 491ILFL494 segment then propagates this signal from Trp495 to Asp490 and induces dissociation of the salt-bridge Asp490-Arg346 and formation of the salt-bridge Glu189-Lys533. The change in salt-bridges alters the motion of KMSKS loop and the editing domain, and eventually triggers the pre-transfer editing pathway. This study provides a model for the molecular trigger of the pre-transfer editing pathway in ValRS, and is useful for further exploring this process.

Domain motions in ValRS·tRNAval·Val-AMP (complex V) and ValRS·tRNAval·Thr-AMP (complex T).

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Acknowledgments

This study was supported in part by the National Natural Science Foundation of China (Grant No. 30570406), the HI-tech Research and Development Program of China (Grant No. 2008AA02Z311), and Shanghai Supercomputer Center of China.

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  1. Li Li

    Present address: Center of Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA

Authors and Affiliations

  1. State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200433, China

    Li Li, Long Yu & Qiang Huang

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  1. Li Li
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  2. Long Yu
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Correspondence to Qiang Huang.

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Li, L., Yu, L. & Huang, Q. Molecular trigger for pre-transfer editing pathway in Valyl-tRNA synthetase: A molecular dynamics simulation study. J Mol Model 17, 555–564 (2011). https://doi.org/10.1007/s00894-010-0754-0

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  • DOI: https://doi.org/10.1007/s00894-010-0754-0

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