Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Drug resistance in gram-negative bacteria may be conferred via efflux through a tripartite complex of an inner membrane pump, an outer membrane pore, and a periplasmic adaptor protein. These are AcrB, TolC, and AcrA, respectively, in Escherichia coli. In Pseudomonas aerugonisa, their homologs are MexB, OprM, and MexA. Defining the interdomain dynamics of the adaptor protein is essential to understanding the mechanism of complex formation. Extended (25 ns) molecular dynamics simulations of MexA have been performed to determine such interdomain dynamics. Analysis of conformational drift demonstrates substantial motions of the three domains of MexA relative to one another. Principal components analysis reveals a hinge-bending motion and rotation of the alpha-helical hairpin relative to the other domains to be the two dominant motions. These two motions provide an element of considerable flexibility which is likely to be exploited in the adaptor function of MexA.

Original publication

DOI

10.1529/biophysj.105.080010

Type

Journal article

Journal

Biophys J

Publication Date

15/07/2006

Volume

91

Pages

558 - 564

Keywords

Bacterial Outer Membrane Proteins, Computer Simulation, Drug Resistance, Bacterial, Membrane Transport Proteins, Models, Molecular, Principal Component Analysis, Protein Structure, Secondary, Protein Structure, Tertiary