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Mol Microbiol. 2010 Oct;78(2):290-304. doi: 10.1111/j.1365-2958.2010.07323.x. Epub 2010 Aug 18.

A structural model of anti-anti-σ inhibition by a two-component receiver domain: the PhyR stress response regulator.

Author information

1
Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, USA. The Committee on Microbiology, The University of Chicago, Chicago, IL, USA.

Abstract

PhyR is a hybrid stress regulator conserved in α-proteobacteria that contains an N-terminal σ-like (SL) domain and a C-terminal receiver domain. Phosphorylation of the receiver domain is known to promote binding of the SL domain to an anti-σ factor. PhyR thus functions as an anti-anti-σ factor in its phosphorylated state. We present genetic evidence that Caulobacter crescentus PhyR is a phosphorylation-dependent stress regulator that functions in the same pathway as σ(T) and its anti-σ factor, NepR. Additionally, we report the X-ray crystal structure of PhyR at 1.25 Å resolution, which provides insight into the mechanism of anti-anti-σ regulation. Direct intramolecular contact between the PhyR receiver and SL domains spans regions σ₂ and σ₄, likely serving to stabilize the SL domain in a closed conformation. The molecular surface of the receiver domain contacting the SL domain is the structural equivalent of α4-β5-α5, which is known to undergo dynamic conformational change upon phosphorylation in a diverse range of receiver proteins. We propose a structural model of PhyR regulation in which receiver phosphorylation destabilizes the intramolecular interaction between SL and receiver domains, thereby permitting regions σ₂ and σ₄ in the SL domain to open about a flexible connector loop and bind anti-σ factor.

PMID:
20735776
PMCID:
PMC2959141
DOI:
10.1111/j.1365-2958.2010.07323.x
[Indexed for MEDLINE]
Free PMC Article

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