TY - JOUR
T1 - Shared TIR enzymatic functions regulate cell death and immunity across the tree of life
AU - Essuman, Kow
AU - Milbrandt, Jeffrey
AU - Dangl, Jeffery L.
AU - Nishimura, Marc T.
N1 - Funding Information:
This work was supported by the National Institutes of Health (grants RF1AG013730, R01NS087632, and R01NS119812 to J.M.), the National Science Foundation (grant IOS-1758400 to J.L.D. and M.T.N.), and HHMI (J.L.D.). J.L.D. is an HHMI investigator. M.T.N. received funding from Syngenta Crop Protection, LLC.
Publisher Copyright:
© 2022 the authors, some rights reserved.
PY - 2022/7/9
Y1 - 2022/7/9
N2 - In the 20th century, researchers studying animal and plant signaling pathways discovered a protein domain that is shared across diverse innate immune systems: the Toll/interleukin-1/resistance gene (TIR) domain. The TIR domain is found in several protein architectures and was defined as an adaptor that mediates protein-protein interactions in animal innate immunity and developmental signaling pathways. However, studies of nerve degeneration in animals—and subsequent breakthroughs in plant, bacterial, and archaeal systems—revealed that TIR domains possess enzymatic activities. We provide a synthesis of TIR functions and the role of various related TIR enzymatic products in evolutionarily diverse immune systems. These studies may ultimately guide interventions that would span the tree of life, from treating human neurodegenerative disorders and bacterial infections to preventing plant diseases.
AB - In the 20th century, researchers studying animal and plant signaling pathways discovered a protein domain that is shared across diverse innate immune systems: the Toll/interleukin-1/resistance gene (TIR) domain. The TIR domain is found in several protein architectures and was defined as an adaptor that mediates protein-protein interactions in animal innate immunity and developmental signaling pathways. However, studies of nerve degeneration in animals—and subsequent breakthroughs in plant, bacterial, and archaeal systems—revealed that TIR domains possess enzymatic activities. We provide a synthesis of TIR functions and the role of various related TIR enzymatic products in evolutionarily diverse immune systems. These studies may ultimately guide interventions that would span the tree of life, from treating human neurodegenerative disorders and bacterial infections to preventing plant diseases.
UR - http://www.scopus.com/inward/record.url?scp=85135234967&partnerID=8YFLogxK
U2 - 10.1126/science.abo0001
DO - 10.1126/science.abo0001
M3 - Review article
C2 - 35857622
AN - SCOPUS:85135234967
SN - 0036-8075
VL - 377
JO - Science
JF - Science
IS - 6605
M1 - eabo0001
ER -