Dynamic interplay between a TonB-dependent heme transporter and a TonB protein in a membrane environment

Abstract

The envelope of Gram-negative bacteria is composed of two membranes separated by the periplasmic space. This organization imposes geometrical and distance constraints that are key for the mechanism of action of multicomponent systems spanning the envelope. However, consideration of all three compartments by experimental approaches is still elusive. Here, we have used the state-of-the-art molecular dynamics simulation in an Escherichia coli envelope model to obtain a dynamic view of molecular interactions between the outer membrane heme transporter HasR and the inner membrane TonB-like protein HasB. Their interaction allows the transfer of the inner membrane proton-motive force derived energy to the transporter for heme internalization. The simulations that incorporate both membranes show the key role of periplasmic domains of both proteins and their dynamics in complex formation and stability. They revealed a previously unidentified network of HasR-HasB protein-protein interactions in the periplasm. Experimental validation (mutations, in vivo phenotypic and biophysical assays) provides support for the simulation-predicted interactions. Based on structural and sequence conservation, the network of interaction revealed in this study is expected to occur in other nutrient import systems.

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ORCID for Syma Khalid: orcid.org/0000-0002-3694-5044

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