Friday, 29 November 2019

Single mutation changes function of bacteria's transporter proteins


Swapping a single amino acid in a simple bacterial protein changes its structure and function, revealing the effects of complex gene evolution, finds a new study published in the journal eLife. The study -- conducted using E. coli bacteria -- can help researchers to better understand the evolution of transporter proteins and their role in drug resistance.

Cells are bound by a thin membrane layer that protects its interior from the outside environment. Within this layer are transporter proteins that control which substances are allowed in and out of the cell. These transporters actively move substances across the cell membrane by loading cargo on one side of the layer, then changing their structure to release it on the other side.

Membrane transporters are typically made up of multiple repeating units. In more complex transporters, the genetic sequence for each of these structural units is fused together into a single gene that codes for the protein.

It is thought that the repeated pattern evolved from smaller membrane protein genes that had duplicated and fused together. But are there evolutionary advantages to having more complex transporters being produced from a single, fused gene?

To investigate this, researchers examined a simple transporter found in E. coli bacteria, which is plentiful in human and animal intestines. However, some strains of E. coli can cause serious illness and are increasingly resistant to antibiotics, which occurs when they pump out toxic compounds using transporters in their membrane. The E. coli transporter, called EmrE, contains two identical protein subunits that work together to move toxic molecules across the membrane and eliminate them from the cell.

Experiments revealed that changing a single amino acid -- the building blocks that make up proteins -- in one of the two protein subunits to make them slightly different from each other dramatically modified the transporter's structure and function. The subtle amino acid swap disrupted the balance of inward- and outward-facing proteins.


Importantly, changing the single amino acid altered the transporter's ability to remove toxic chemicals from E. coli and reduced the bacteria's resistance to drugs -- which may have future implications for drug development and combating antibiotic resistance.

The researchers note that the effects of a minor change to one of the identical halves of the EmrE transporter demonstrates how sensitive membrane transporters are to mutations.

See:

Maureen Leninger, Ampon Sae Her, Nathaniel J Traaseth. Inducing conformational preference of the membrane protein transporter EmrE through conservative mutations. eLife, 2019; 8 DOI: 10.7554/eLife.48909

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

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