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|Title:||The RIG-I ATPase core has evolved a functional requirement for allosteric stabilization by the Pincer domain||Authors:||Rawling, David C.
Kohlway, Andrew S.
Ding, Steve C.
Pyle, Anna Marie
|Keywords:||DRNTU::Science::Medicine||Issue Date:||2014||Source:||Rawling, D. C., Kohlway, A. S., Luo, D., Ding, S. C., & Pyle, A. M. (2014). The RIG-I ATPase core has evolved a functional requirement for allosteric stabilization by the Pincer domain. Nucleic acids research, 42(18), 11601-11611.||Series/Report no.:||Nucleic acids research||Abstract:||Retinoic acid-inducible gene I (RIG-I) is a pattern recognition receptor expressed in metazoan cells that is responsible for eliciting the production of type I interferons and pro-inflammatory cytokines upon detection of intracellular, non-self RNA. Structural studies of RIG-I have identified a novel Pincer domain composed of two alpha helices that physically tethers the C-terminal domain to the SF2 helicase core. We find that the Pincer plays an important role in mediating the enzymatic and signaling activities of RIG-I. We identify a series of mutations that additively decouple the Pincer motif from the ATPase core and show that this decoupling results in impaired signaling. Through enzymological and biophysical analysis, we further show that the Pincer domain controls coupled enzymatic activity of the protein through allosteric control of the ATPase core. Further, we show that select regions of the HEL1 domain have evolved to potentiate interactions with the Pincer domain, resulting in an adapted ATPase cleft that is now responsive to adjacent domains that selectively bind viral RNA.||URI:||https://hdl.handle.net/10356/103799
|ISSN:||0305-1048||DOI:||10.1093/nar/gku817||Rights:||© 2014 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||LKCMedicine Journal Articles|
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