Abstract
Membrane proteins are frequently present in crowded environments, which favour lateral association and, on occasions, two-dimensional crystallization. To better understand the non-specific lateral association of a membrane protein we have characterized the free energy landscape for the dimerization of a bacterial outer membrane protein, NanC, in a phospholipid bilayer membrane. NanC is a member of the KdgM-family of bacterial outer membrane proteins and is responsible for sialic acid transport in E. coli. Umbrella sampling and coarse-grained molecular dynamics were employed to calculate the potentials of mean force (PMF) for a variety of restrained relative orientations of two NanC proteins as the separation of their centres of mass was varied. We found the free energy of dimerization for NanC to be in the range of to . Differences in the depths of the PMFs for the various orientations are related to the shape of the proteins. This was quantified by calculating the lipid-inaccessible buried surface area of the proteins in the region around the minimum of each PMF. The depth of the potential well of the PMF was shown to depend approximately linearly on the buried surface area. We were able to resolve local minima in the restrained PMFs that would not be revealed using conventional umbrella sampling. In particular, these features reflected the local organization of the intervening lipids between the two interacting proteins. Through a comparison with the distribution of lipids around a single freely-diffusing NanC, we were able to predict the location of these restrained local minima for the orientational configuration in which they were most pronounced. Our ability to make this prediction highlights the important role that lipid organization plays in the association of two NanCs in a bilayer.
Highlights
Cellular membranes separate the contents of a cell from its surroundings, they play a key role in cell regulation and metabolism
Cells are surrounded by selectively-permeable bilayer membranes, enabling the cell to control its internal environment. Embedded within these membranes are a variety of membrane proteins, many of which facilitate this environmental control and are integral to numerous metabolic processes. Their location within the membrane and their mutual association are controlled by many factors
We use molecular dynamics simulations to investigate the free energy of association for a pair of relatively simple membrane proteins
Summary
Cellular membranes separate the contents of a cell from its surroundings, they play a key role in cell regulation and metabolism. The outer membrane lipid bilayer is composed of phospholipids in the inner (i.e. periplasmic) leaflet, and of lipopolysaccharides in the outer leaflet. Within this membrane are many species of outer membrane proteins (OMPs), a class of integral membrane proteins whose secondary structures are almost exclusively b{barrels [2]. Many of these b{barrels are porins (OmpC, OmpF, LamB, NanC, for example), through which small (approximately 500 g mol-1) molecules can diffuse across the membrane. Porins provide a route for many antibiotics into bacterial cells and are potential vaccine targets [3]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
