Author:
van den Berg Bert,Prathyusha Bhamidimarri Satya,Dahyabhai Prajapati Jigneshkumar,Kleinekathöfer Ulrich,Winterhalter Mathias
Abstract
The outer membrane (OM) of gram-negative bacteria forms a protective layer around the cell that serves as a permeability barrier to prevent unrestricted access of noxious substances. The permeability barrier of the OM results partly from the limited pore diameters of OM diffusion channels. As a consequence, there is an “OM size-exclusion limit,” and the uptake of bulky molecules with molecular masses of more than ∼600 Da is thought to be mediated by TonB-dependent, active transporters. Intriguingly, the OM protein CymA fromKlebsiella oxytocadoes not depend on TonB but nevertheless mediates efficient OM passage of cyclodextrins with diameters of up to ∼15 Å. Here we show, by using X-ray crystallography, molecular dynamics simulations, and single-channel electrophysiology, that CymA forms a monomeric 14-stranded β-barrel with a large pore that is occluded on the periplasmic side by the N-terminal 15 residues of the protein. Representing a previously unidentified paradigm in OM transport, CymA mediates the passive diffusion of bulky molecules via an elegant transport mechanism in which a mobile element formed by the N terminus acts as a ligand-expelled gate to preserve the permeability barrier of the OM.
Publisher
Proceedings of the National Academy of Sciences
Cited by
70 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献