Saliva-based SARS-CoV-2 antibody testing

As the Atlanta area recovers from Zeta, we’d like to highlight this Journal of Clinical Microbiology paper about saliva-based SARS-CoV-2 antibody testing. It was a collaboration between the Hope Clinic and investigators at Johns Hopkins, led by epidemiologist Christopher Heaney. Infectious disease specialists Matthew Collins, Nadine Rouphael and several colleagues from Emory are co-authors. They organized the collection of saliva and blood samples from Emory COVID-19 patients at several stages: being tested, hospitalized, and recovered. Read more

Peeling away pancreatic cancers' defenses

A combination immunotherapy approach that gets through pancreatic cancers’ extra Read more

Immune cell activation in severe COVID-19 resembles lupus

In severe cases of COVID-19, Emory researchers have been observing an exuberant activation of B cells, resembling acute flares in systemic lupus erythematosus (SLE), an autoimmune disease. The findings point towards tests that could separate some COVID-19 patients who need immune-calming therapies from others who may not. It also may begin to explain why some people infected with SARS-CoV-2 produce abundant antibodies against the virus, yet experience poor outcomes. The results were published online on Oct. Read more

mometasone

Resurrecting an ancient receptor to understand a modern drug

To make progress in structural biology, look millions of years into the past. Emory biochemist Eric Ortlund and his colleagues have been taking the approach of “resurrecting” ancient proteins to get around difficulties in probing their structures.

Steroid receptor evolution

Ortlund’s laboratory recently published a paper in Journal of Biological Chemistry describing the structure of a protein that is supposed to have existed 450 million years ago, in a complex with an anti-inflammatory drug widely used today. MSP graduate student Jeffrey Kohn is the first author.

Mometasone furoate is the active ingredient of drugs used to treat asthma, allergies and skin irritation. It is part of a class of drugs known as glucocorticoids, which can have a host of side effects such as reduced bone density and elevated blood sugar or blood pressure with long-term use.

One reason for these side effects is because the steroid receptor proteins that allow cells to detect and respond to hormones such as estrogen, testosterone, aldosterone and cortisol are all related. Mometasone is a good example of how glucocorticoids cross-react, Ortlund says. That made it an ideal test of the technique of mixing ancient receptors with modern drugs.

“We used this structure to determine why mometasone cross reacts with the progesterone receptor, which regulates fertility, and why it inhibits the mineralocorticoid receptor, which regulates blood pressure,” he says.

Mometasone furoate in complex with the ancient receptor

Scientists have examined the sequences of the genes that encode these proteins at several points on the evolutionary tree, and used the information to reconstruct what the ancestral receptor looked like. This helps solve some problems that biochemists studying these proteins have had to deal with. One of these is: changing one amino acid in the protein sometimes means that the whole protein malfunctions.

“The ancestral receptors are more tolerant to mutation, and they are more promiscuous with respect to activation,” Ortlund says. “That is, they tend to respond to a wider array of endogenous steroid hormones, which makes sense in an evolutionary context. This enhanced activation profile and tolerance to mutation is what we feel makes them ideally suited to structure-function studies.”

The blog Panda’s Thumb has an interesting discussion of this area of research, in relation to the larger question of how proteins evolve.

Posted on by Quinn Eastman in Uncategorized Leave a comment