Completed Cells, Biochemistry & Physiology Genetics & Molecular Biology

Structural basis of use of ion flow across the bacterial inner membrane to power secretion and motility

In plain English

AI plain-English summary

Bacteria use the same basic rotating motor to pump toxins into our cells and to spin their flagella to swim. This matters because many disease-causing bacteria rely on these ion-powered machines to infect us. The researcher has discovered that several different bacterial machines—ones that secrete toxins, import nutrients, and drive swimming—share an unexpected common architecture in the parts embedded in the inner membrane. This shared design suggests a rotating mechanism may be at work. The project will test this hypothesis by determining how a single type of ion flow can be adapted to perform such different jobs on both sides of the membrane. This is fundamental science. If the rotating mechanism is confirmed, it would reveal a unifying principle for how bacteria power infection and survival. In the longer term, understanding this shared architecture could open the door to designing drugs that jam the motor common to multiple bacterial machines at once—potentially crippling both toxin delivery and motility in a single treatment. Past discoveries of shared bacterial machinery, such as the type III secretion system, have already led to vaccine targets.

View original technical description
Bacteria need to control import/export of charged molecules across their relatively impermeable membrane(s) which also house many nano-machines critical for motility and hence infection. These processes are often driven by harvesting the energy stored in ion gradients across the inner-membrane by ion flow through inner-membrane resident channels. Unpublished work from my group has demonstrated that bacterial inner-membrane ion channels which couple ion flow to protein secretion, nutrient import and bacterial motility unexpectedly share a common architecture within their membrane domains. The architecture revealed unexpectedly suggests rotation between components may be mechanistically important and this application seeks to test this hypothesis. The question will be assessed by a series of structural and mechanistic studies that will seek to determine what commonalities in mechanism underlie this shared architecture and how this is adapted to perform the very different biologies achieved. Specifically, what adaptations allow coupling of uni-directional ion flow to achieve work on both sides of the inner-membrane. Using structural and functional tools developed in my group we will study the ion channels in more native contexts both in terms of the membrane bilayer and in terms of the protein interactions that couple ion flow to work to tease out molecular mechanisms.

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Researchers

Susan Lea (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

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Visualising transport dynamics of transmembrane pumps
Desiphering the structural origins of functional multimodality in bacterial mechanosensitive ion channels
A biochemical and biophysical analysis of a ubiquitous protein translocation apparatus
Structure, Dynamics and Activity of the Bacterial Secretosome

Original classification

Investigator Award in Science

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