Structural and Mechanistic Regulation of the Pro-degenerative NAD Hydrolase SARM1

Matthew Bratkowski, Tian Xie, Desiree A. Thayer, Shradha Lad, Prakhyat Mathur, Yu San Yang, Gregory Danko, Thomas C. Burdett, Jean Danao, Aaron Cantor, Jennifer A. Kozak, Sean P. Brown, Xiaochen Bai, Shilpa Sambashivan

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Bratkowski et al. describe cryo-EM structures of autoinhibited and active SARM1, an axon-enriched, injury-activated NADase. Structure-function studies elucidate the mode of autoinhibition and SARM1 activity regulation. The authors provide mechanistic insight into SARM1’s regulation by the local metabolic environment, laying the foundation for future SARM1-based therapies to treat neurological diseases.

Original languageEnglish (US)
Article number107999
JournalCell Reports
Volume32
Issue number5
DOIs
StatePublished - Aug 4 2020

Keywords

  • NAD hydrolase
  • NAM
  • NMN
  • SARM1
  • autoinhibition
  • axon
  • axonopathies
  • cryo-EM

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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