Document Type
Article
Publication Date
2018
College/Unit
School of Medicine
Department/Program/Center
Biochemistry
Abstract
Protein degradation in all domains of life requires ATPases that unfold and inject proteins into compartmentalized proteolytic chambers. Proteasomal ATPases in eukaryotes and archaea contain poorly understood N-terminally conserved coiled-coil domains. In this study, we engineer disulfide crosslinks in the coiled-coils of the archaeal proteasomal ATPase (PAN) and report that its three identical coiled-coil domains can adopt three different conforma- tions: (1) in-register and zipped, (2) in-register and partially unzipped, and (3) out-of-register. This conformational heterogeneity conflicts with PAN’s symmetrical OB-coiled-coil crystal structure but resembles the conformational heterogeneity of the 26S proteasomal ATPases’ coiled-coils. Furthermore, we find that one coiled-coil can be conformationally constrained even while unfolding substrates, and conformational changes in two of the coiled-coils reg- ulate PAN switching between resting and active states. This switching functionally mimics similar states proposed for the 26S proteasome from cryo-EM. These findings thus build a mechanistic framework to understand regulation of proteasome activity.
Digital Commons Citation
Snoberger, Aaron; Brettrager, Evan J.; and Smith, David M., "Conformational switching in the coiled-coil domains of a proteasomal ATPase regulates substrate processing" (2018). Faculty & Staff Scholarship. 1530.
https://researchrepository.wvu.edu/faculty_publications/1530
Source Citation
Snoberger, A., Brettrager, E. J., & Smith, D. M. (2018). Conformational switching in the coiled-coil domains of a proteasomal ATPase regulates substrate processing. Nature Communications, 9(1). https://doi.org/10.1038/s41467-018-04731-6
Included in
Medical Biochemistry Commons, Medical Toxicology Commons, Pharmacy and Pharmaceutical Sciences Commons
Comments
Open Access This article is licensed under a Creative Commons
Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.
© The Author(s) 2018