Insights into the key determinants of membrane protein topology enable the identification of new monotopic folds
- Massachusetts Institute of Technology, United States
- Centro de Investigaciones Biológicas - CIB-CSIC, Spain
Abstract
Monotopic membrane proteins integrate into the lipid bilayer via reentrant hydrophobic domains that enter and exit on a single face of the membrane. Whereas many membrane-spanning proteins have been structurally characterized and transmembrane topologies can be predicted computationally, relatively little is known about the determinants of membrane topology in monotopic proteins. Recently, we reported the X-ray structure determination of PglC, a full-length monotopic membrane protein with phosphoglycosyl transferase (PGT) activity. The definition of this unique structure has prompted in vivo, biochemical, and computational analyses to understand and define two key motifs that contribute to the membrane topology and to provide insight into the dynamics of the enzyme in a lipid bilayer environment. Using the new information gained from studies on the PGT superfamily we demonstrate that the two motifs exemplify principles of topology determination that can be applied to the identification of reentrant domains among diverse monotopic proteins of interest.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Jean-Marie Swiecicki
Funding
NIH Office of the Director (NIH GM-039334)
- Sonya Entova
- Barbara Imperiali
Ministerio de Economía y Competitividad (CTQ2014-57141-R)
- Jean-Marc Billod
- Sonsoles Martin-Santamaria
Jane Coffin Childs Memorial Fund for Medical Research
- Jean-Marie Swiecicki
NIH Office of the Director (T32-GM007287)
- Sonya Entova
Ministerio de Economía y Competitividad (CTQ2017-88353-R)
- Jean-Marc Billod
- Sonsoles Martin-Santamaria
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Entova et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Insights into the key determinants of membrane protein topology enable the identification of new monotopic folds
eLife 7:e40889.
https://doi.org/10.7554/eLife.40889
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