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.
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:
Posted by Dr. Tim Sandle, Pharmaceutical Microbiology
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