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Elife. 2014 Sep 2;3:e03650. doi: 10.7554/eLife.03650.

Mechanistic insight into the conserved allosteric regulation of periplasmic proteolysis by the signaling molecule cyclic-di-GMP.

Author information

1
Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, United States.
2
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, United States.
3
Department of Biochemistry and Biophysics, Oregon State University, Corvallis, United States.
4
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, United States georgeo@dartmouth.edu.
5
Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, United States hs293@cornell.edu.

Abstract

Stable surface adhesion of cells is one of the early pivotal steps in bacterial biofilm formation, a prevalent adaptation strategy in response to changing environments. In Pseudomonas fluorescens, this process is regulated by the Lap system and the second messenger cyclic-di-GMP. High cytoplasmic levels of cyclic-di-GMP activate the transmembrane receptor LapD that in turn recruits the periplasmic protease LapG, preventing it from cleaving a cell surface-bound adhesin, thereby promoting cell adhesion. In this study, we elucidate the molecular basis of LapG regulation by LapD and reveal a remarkably sensitive switching mechanism that is controlled by LapD's HAMP domain. LapD appears to act as a coincidence detector, whereby a weak interaction of LapG with LapD transmits a transient outside-in signal that is reinforced only when cyclic-di-GMP levels increase. Given the conservation of key elements of this receptor system in many bacterial species, the results are broadly relevant for cyclic-di-GMP- and HAMP domain-regulated transmembrane signaling.

KEYWORDS:

bacterial pathogens; biofilm formation; c-di-GMP; cell adhesion; signaling; transmembrane protein

PMID:
25182848
PMCID:
PMC4359373
DOI:
10.7554/eLife.03650
[Indexed for MEDLINE]
Free PMC Article

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