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IMAGE: A cell in yellow is shown dying by necroptosis, a process requiring the protein MLKL view more
Credit: WEHI Australia
A new molecular freeze frame technique has allowed WEHI researchers to see key steps in how the protein MLKL kills cells.
Small proteins called monobodies were used to freeze MLKL at different stages as it moved from a dormant to an activated state, a key process that enables an inflammatory form of cell death called necroptosis. The team were able to map how the three-dimensional structure of MLKL changed, revealing potential target sites that might be targets for drugs - a potential new approach to blocking necroptosis as a treatment for inflammatory diseases.
Columbia University Irving Medical Center
A new imaging technique developed by scientists at Columbia University Vagelos College of Physicians and Surgeons and St. Jude Children’s Research Hospital captures movies of receptors on the surface of living cells in unprecedented detail and could pave the way to a trove of new drugs.
The researchers used the technique to zoom in on individual receptor proteins on the surface of living cells to determine if the receptors work solo or come together to work as pairs. This work appeared in the April issue of Nature Methods.
“If two different receptors come together to form a dimer with distinctive function and pharmacology, this might allow for a new generation of drugs with greater specificity and reduced side effects.”
The candidates that have been considered include remdesivir, originally developed to treat hepatitis C and Ebola. But Nature says that “some clinical studies have failed to confirm that it offers [Covid] patients any benefit. And the drug is expensive, difficult to manufacture and must be given intravenously in a hospital - all undesirable attributes in the middle of a pandemic.”
Experts are hoping that some of those issues might be avoided with another antiviral drug, molnupiravir, which is undergoing late-stage clinical testing as a Covid treatment by the US National Institutes of Health (NIH). Meanwhile, the NHS is testing an antiviral called favipiravir in trials involving UK patients.
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