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Abstract The flagellar motor is a powerful macromolecular machine used to propel bacteria through various environments. We determined that flagellar motility of the alpha‐proteobacteriumSinorhizobium melilotiis nearly abolished in the absence of the transcriptional regulator LdtR, known to influence peptidoglycan remodeling and stress response. LdtR does not regulate motility gene transcription. Remarkably, the motility defects of the ΔldtRmutant can be restored by secondary mutations in the motility genemotAor a previously uncharacterized gene in the flagellar regulon, which we namedmotS. MotS is not essential forS. melilotimotility and may serve an accessory role in flagellar motor function. Structural modeling predicts that MotS comprised an N‐terminal transmembrane segment, a long‐disordered region, and a conserved β‐sandwich domain. The C terminus of MotS is localized in the periplasm. Genetics based substitution of MotA with MotAG12Salso restored the ΔldtRmotility defect. The MotAG12Svariant protein features a local polarity shift at the periphery of the MotAB stator units. We propose that MotS may be required for optimal alignment of stators in wild‐type flagellar motors but becomes detrimental in cells with altered peptidoglycan. Similarly, the polarity shift in stator units composed of MotB/MotAG12Smight stabilize its interaction with altered peptidoglycan.
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FARS2 mutations presenting with pure spastic paraplegia and lesions of the dentate nuclei
Abstract Mutations inFARS2, the gene encoding the mitochondrial phenylalanine‐tRNA synthetase (mtPheRS), have been linked to a range of phenotypes including epileptic encephalopathy, developmental delay, and motor dysfunction. We report a 9‐year‐old boy with novel compound heterozygous variants ofFARS2, presenting with a pure spastic paraplegia syndrome associated with bilateral signal abnormalities in the dentate nuclei. Exome sequencing identified a paternal nonsense variant (Q216X) lacking the catalytic core and anticodon‐binding regions, and a maternal missense variant (P136H) possessing partial enzymatic activity. This case confirms and expands the phenotype related toFARS2mutations with regards to clinical presentation and neuroimaging findings.
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- Award ID(s):
- 1715840
- PAR ID:
- 10068149
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Annals of Clinical and Translational Neurology
- Volume:
- 5
- Issue:
- 9
- ISSN:
- 2328-9503
- Page Range / eLocation ID:
- p. 1128-1133
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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