Journal article
Structural basis of autoregulatory scaffolding by apoptosis signal-regulating kinase 1
JF Weijman, A Kumar, SA Jamieson, CM King, TT Caradoc-Davies, EC Ledgerwood, JM Murphy, PD Mace
Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2017
Abstract
Apoptosis signal-regulating kinases (ASK1-3) are apical kinases of the p38 and JNK MAP kinase pathways. They are activated by diverse stress stimuli, including reactive oxygen species, cytokines, and osmotic stress; however, a molecular understanding of how ASK proteins are controlled remains obscure. Here, we report a biochemical analysis of the ASK1 kinase domain in conjunction with its N-Terminal thioredoxin-binding domain, along with a central regulatory region that links the two. We show that in solution the central regulatory region mediates a compact arrangement of the kinase and thioredoxin-binding domains and the central regulatory region actively primes MKK6, a key ASK1 substrate, ..
View full abstractGrants
Awarded by Victorian State Government Operational Infrastructure Support, National Health and Medical Research Council (NHMRC) Independent Research Institute Infrastructure Support Scheme
Awarded by NHMRC Fellowship
Awarded by National Health and Medical Research Council of Australia
Funding Acknowledgements
We thank the New Zealand synchrotron group for facilitating access to the MX beamlines, the staff at the MX and SAXS beamlines for their assistance with data collection, and Dr. Torsten Kleffmann for mass spectrometry analysis. P.D.M. and J.F.W. are currently supported by a Rutherford Discovery Fellowship from the New Zealand government administered by the Royal Society of New Zealand (to P.D.M.). Additional support was provided by University of Otago research grants (to P.D.M.), the Victorian State Government Operational Infrastructure Support, National Health and Medical Research Council (NHMRC) Independent Research Institute Infrastructure Support Scheme Grant 9000220, and NHMRC Fellowship 1105754 (to J.M.M.). This research was undertaken on both the macromolecular crystallography (MX1 and MX2) and small-angle X-ray scattering beamlines at the Australian Synchrotron.