Journal
CELL BIOCHEMISTRY AND BIOPHYSICS
Volume 77, Issue 1, Pages 79-87Publisher
HUMANA PRESS INC
DOI: 10.1007/s12013-018-0851-8
Keywords
Phospholipase; EPR; Spin labeling; ExoU; Pseudomonas aeruginosa
Funding
- National Institutes of Health [GM114234, AI104922]
- NIH [S10RR022422, S10OD011937]
Ask authors/readers for more resources
Numerous pathogenic bacteria produce proteins evolved to facilitate their survival and dissemination by modifying the host environment. These proteins, termed effectors, often play a significant role in determining the virulence of the infection. Consequently, bacterial effectors constitute an important class of targets for the development of novel antibiotics. ExoU is a potent phospholipase effector produced by the opportunistic pathogen Pseudomonas aeruginosa. Previous studies have established that the phospholipase activity of ExoU requires non-covalent interaction with ubiquitin, however the molecular details of the mechanism of activation and the manner in which ExoU associates with a target lipid bilayer are not understood. In this review we describe our recent studies using site-directed spin labeling (SDSL) and EPR spectroscopy to elucidate the conformational changes and membrane interactions that accompany activation of ExoU. We find that ubiquitin binding and membrane interaction act synergistically to produce structural transitions that occur upon ExoU activation, and that the C-terminal four-helix bundle of ExoU functions as a phospholipid-binding domain, facilitating the association of ExoU with the membrane surface.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available