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

ELife
Niels BradshawRichard Losick

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 fromBacillus 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.

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Citations

Feb 3, 2018·Environmental Microbiology Reports·Sophie BouilletChantal Iobbi-Nivol
Mar 12, 2019·Future Microbiology·Imrich BarákNaďa Labajová
Apr 13, 2019·Genes & Development·Victoria DorichAlexandra M Deaconescu
Sep 29, 2021·EMBO Reports·Dieter WaschbüschAmir R Khan

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Methods Mentioned

BETA
X-ray
size exclusion chromatography
light scattering
size-exclusion chromatography

Software Mentioned

DALI
REFMAC
COOT
HHPRED
HKL
SuperSegger
PHENIX
MOLREP
MatLab scripts

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