Nature Communications (Jun 2022)

Structural basis for defective membrane targeting of mutant enzyme in human VLCAD deficiency

  • Michelle S. Prew,
  • Christina M. Camara,
  • Thomas Botzanowski,
  • Jamie A. Moroco,
  • Noah B. Bloch,
  • Hannah R. Levy,
  • Hyuk-Soo Seo,
  • Sirano Dhe-Paganon,
  • Gregory H. Bird,
  • Henry D. Herce,
  • Micah A. Gygi,
  • Silvia Escudero,
  • Thomas E. Wales,
  • John R. Engen,
  • Loren D. Walensky

DOI
https://doi.org/10.1038/s41467-022-31466-2
Journal volume & issue
Vol. 13, no. 1
pp. 1 – 12

Abstract

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Prew et al. uncovered a structural basis for human VLCAD deficiency that arises from point mutations within the enzyme’s membrane-binding region, which was shown to fold as a putative α-helical hairpin. Helix-breaking mutations selectively disrupt membrane interaction and thus homeostatic function.