skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: A widespread family of serine/threonine protein phosphatases shares a common regulatory switch with proteasomal proteases

Abstract

PP2C phosphatases control biological processes including stress responses, development, and cell division in all kingdoms of life. Diverse regulatory domains adapt PP2C phosphatases to specific functions, but how these domains control phosphatase activity was unknown. We present structures representing active and inactive states of the PP2C phosphatase SpoIIE from Bacillus subtilis. Based on structural analyses and genetic and biochemical experiments, we identify an α-helical switch that shifts a carbonyl oxygen into the active site to coordinate a metal cofactor. Our analysis indicates that this switch is widely conserved among PP2C family members, serving as a platform to control phosphatase activity in response to diverse inputs. Remarkably, the switch is shared with proteasomal proteases, which we identify as evolutionary and structural relatives of PP2C phosphatases. Although these proteases use an unrelated catalytic mechanism, rotation of equivalent helices controls protease activity by movement of the equivalent carbonyl oxygen into the active site.

Authors:
ORCiD logo [1];  [2]; ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [2]; ORCiD logo [1]
  1. Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States
  2. Structural Biology Laboratory, Department of Chemistry, University of York, York, United Kingdom
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
NIHOTHER
OSTI Identifier:
1390882
Resource Type:
Journal Article
Resource Relation:
Journal Name: eLife; Journal Volume: 6; Journal Issue: 05, 2017
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Bradshaw, Niels, Levdikov, Vladimir M., Zimanyi, Christina M., Gaudet, Rachelle, Wilkinson, Anthony J., and Losick, Richard. A widespread family of serine/threonine protein phosphatases shares a common regulatory switch with proteasomal proteases. United States: N. p., 2017. Web. doi:10.7554/eLife.26111.
Bradshaw, Niels, Levdikov, Vladimir M., Zimanyi, Christina M., Gaudet, Rachelle, Wilkinson, Anthony J., & Losick, Richard. A widespread family of serine/threonine protein phosphatases shares a common regulatory switch with proteasomal proteases. United States. doi:10.7554/eLife.26111.
Bradshaw, Niels, Levdikov, Vladimir M., Zimanyi, Christina M., Gaudet, Rachelle, Wilkinson, Anthony J., and Losick, Richard. Sat . "A widespread family of serine/threonine protein phosphatases shares a common regulatory switch with proteasomal proteases". United States. doi:10.7554/eLife.26111.
@article{osti_1390882,
title = {A widespread family of serine/threonine protein phosphatases shares a common regulatory switch with proteasomal proteases},
author = {Bradshaw, Niels and Levdikov, Vladimir M. and Zimanyi, Christina M. and Gaudet, Rachelle and Wilkinson, Anthony J. and Losick, Richard},
abstractNote = {PP2C phosphatases control biological processes including stress responses, development, and cell division in all kingdoms of life. Diverse regulatory domains adapt PP2C phosphatases to specific functions, but how these domains control phosphatase activity was unknown. We present structures representing active and inactive states of the PP2C phosphatase SpoIIE from Bacillus subtilis. Based on structural analyses and genetic and biochemical experiments, we identify an α-helical switch that shifts a carbonyl oxygen into the active site to coordinate a metal cofactor. Our analysis indicates that this switch is widely conserved among PP2C family members, serving as a platform to control phosphatase activity in response to diverse inputs. Remarkably, the switch is shared with proteasomal proteases, which we identify as evolutionary and structural relatives of PP2C phosphatases. Although these proteases use an unrelated catalytic mechanism, rotation of equivalent helices controls protease activity by movement of the equivalent carbonyl oxygen into the active site.},
doi = {10.7554/eLife.26111},
journal = {eLife},
number = 05, 2017,
volume = 6,
place = {United States},
year = {Sat May 20 00:00:00 EDT 2017},
month = {Sat May 20 00:00:00 EDT 2017}
}