Structural Evidence for an Octameric Ring Arrangement of SARM1.
SAM domain
SARM1
cell death
electron microscopy
x-ray crystallography
Journal
Journal of molecular biology
ISSN: 1089-8638
Titre abrégé: J Mol Biol
Pays: Netherlands
ID NLM: 2985088R
Informations de publication
Date de publication:
06 09 2019
06 09 2019
Historique:
received:
25
04
2019
revised:
16
06
2019
accepted:
25
06
2019
pubmed:
7
7
2019
medline:
17
6
2020
entrez:
7
7
2019
Statut:
ppublish
Résumé
SARM1 induces axonal degeneration in response to various insults and is therefore considered an attractive drug target for the treatment of neuro-degenerative diseases as well as for brain and spinal cord injuries. SARM1 activity depends on the integrity of the protein's SAM domains, as well as on the enzymatic conversion of NAD+ to ADPR (ADP Ribose) products by the SARM1's TIR domain. Therefore, inhibition of either SAM or TIR functions may constitute an effective therapeutic strategy. However, there is currently no SARM1-directed therapeutic approach available because of an insufficient structural and mechanistic understanding of this protein. In this study, we found that SARM1 assembles into an octameric ring. This arrangement was not described before in other SAM proteins, but is reminiscent of the apoptosome and inflammasome-well-known apoptotic ring-like oligomers. We show that both SARM1 and the isolated tandem SAM
Identifiants
pubmed: 31278906
pii: S0022-2836(19)30419-X
doi: 10.1016/j.jmb.2019.06.030
pii:
doi:
Substances chimiques
Armadillo Domain Proteins
0
Cytoskeletal Proteins
0
SARM1 protein, human
0
Solutions
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3591-3605Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.