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

doi:10.1016/j.celrep.2020.107999

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 journal › Article › peer-review

78 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 language	English (US)
Article number	107999
Journal	Cell Reports
Volume	32
Issue number	5
DOIs	https://doi.org/10.1016/j.celrep.2020.107999
State	Published - Aug 4 2020

Keywords

NAD hydrolase
NAM
NMN
SARM1
autoinhibition
axon
axonopathies
cryo-EM

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2020.107999

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title = "Structural and Mechanistic Regulation of the Pro-degenerative NAD Hydrolase SARM1",

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{\textquoteright}s regulation by the local metabolic environment, laying the foundation for future SARM1-based therapies to treat neurological diseases.",

keywords = "NAD hydrolase, NAM, NMN, SARM1, autoinhibition, axon, axonopathies, cryo-EM",

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doi = "10.1016/j.celrep.2020.107999",

language = "English (US)",

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AU - Bratkowski, Matthew

AU - Xie, Tian

AU - Thayer, Desiree A.

AU - Lad, Shradha

AU - Mathur, Prakhyat

AU - Yang, Yu San

AU - Danko, Gregory

AU - Burdett, Thomas C.

AU - Danao, Jean

AU - Cantor, Aaron

AU - Kozak, Jennifer A.

AU - Brown, Sean P.

AU - Bai, Xiaochen

AU - Sambashivan, Shilpa

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AB - 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.

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KW - axon

KW - axonopathies

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

Abstract

Keywords

ASJC Scopus subject areas

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