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

DOI: 10.7554/eLife.26111 DOI Help

Authors: Niels Bradshaw (Harvard University) , Vladimir M. Levdikov (University of York) , Christina M Zimanyi (New York Structural Biology Center) , Rachelle Gaudet (Harvard University) , Anthony J. Wilkinson (University of York) , Richard Losick (Harvard University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Elife , VOL 6

State: Published (Approved)
Published: May 2017
Diamond Proposal Number(s): 7864

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.

Journal Keywords: Genomics and Evolutionary Biology; Microbiology and Infectious Disease; B. subtilis

Subject Areas: Biology and Bio-materials

Instruments: I02-Macromolecular Crystallography