Mutations in MARS identified in a specific type of pulmonary alveolar proteinosis alter methionyl-tRNA synthetase activity

The FEBS Journal
Martine ComissoMarc Mirande

Abstract

Biallelic missense mutations in MARS are responsible for rare but severe cases of pulmonary alveolar proteinosis (PAP) prevalent on the island of La Réunion. MARS encodes cytosolic methionyl-tRNA synthetase (MetRS), an essential translation factor. The multisystemic effects observed in patients with this form of PAP are consistent with a loss-of-function defect in an ubiquitously expressed enzyme. The pathophysiological mechanisms involved in MARS-related PAP are currently unknown. In this work, we analyzed the effect of the PAP-related mutations in MARS on the thermal stability and on the catalytic parameters of the MetRS mutants, relative to wild-type. The effect of these mutations on the structural integrity of the enzyme as a member of the cytosolic multisynthetase complex was also investigated. Our results establish that the PAP-related substitutions in MetRS impact the tRNAMet -aminoacylation reaction especially at the level of methionine recognition, and suggest a direct link between the loss of activity of the enzyme and the pathological disorders in PAP.

References

Aug 31, 2000·Annual Review of Biochemistry·M Ibba, D Soll
Feb 17, 2001·The Journal of Physiology·T Hoshi, S Heinemann
Dec 26, 2003·The New England Journal of Medicine·Bruce C TrapnellKoh Nakata
Sep 13, 2005·Nature Structural & Molecular Biology·Kotaro NakanishiOsamu Nureki
May 17, 2006·The Journal of Nutrition·Peter J Garlick
Jan 10, 2009·The Journal of Biological Chemistry·Monika KaminskaMarc Mirande
Feb 19, 2013·Nature Chemical Biology·Min Guo, Paul Schimmel
Feb 22, 2013·EMBO Molecular Medicine·Peng Yao, Paul L Fox
Jun 5, 2013·Journal of Neurology, Neurosurgery, and Psychiatry·Michael GonzalezUNKNOWN Inherited Neuropathy Consortium
Jun 15, 2014·Orphanet Journal of Rare Diseases·Laurent EnaudJacques de Blic
Oct 17, 2015·The Journal of Biological Chemistry·Ha Yeon ChoSunghoon Kim

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Citations

Oct 3, 2018·World Journal of Gastroenterology : WJG·Kuerbanjiang AbuduxikuerJian-She Wang
Oct 30, 2020·European Respiratory Review : an Official Journal of the European Respiratory Society·Alice HadchouelJacques de Blic

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