Immunity system complexity: gasdermin-B reviewed (Introduction)

by David Turell , Thursday, March 30, 2023, 18:45 (387 days ago) @ David Turell

A very important part of our immune system:

https://phys.org/news/2023-03-protein-effectiveness-bacteria.html

"Previous research had looked at how Shigella interacts with gasdermin-B, a critical part of our immune system that helps protect us against infection. Gasdermin-B is member of a protein family called gasdermin, which includes gasdermin-A, -B, -C, -D, -E and -F. It was thought that when gasdermin-B detects an invader, such as bacteria, it begins to poke holes in the cell's wall, causing it to burst open and release chemicals that induce inflammation and call reinforcements from the immune system. But the past research studies on gasdermin-B were contradictory; some confirmed its role in cell death during infection, but others contradicted the idea.

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"Their research confirms previous research and provides evidence that Shigella bacteria grab onto a specific segment of gasdermin-B in humans. However, the mouse version of the protein has a different shape that prevents Shigella from latching onto it, resulting in the rapid clearance of the bacteria and preventing infection. This finding helps explain why Shigella is unable to infect mice.

"Since human gasdermin-B can be configured in six slightly differing proteins, or isoforms, the team expressed all six then looked at how these isoforms behaved inside cells, and they found something surprising: some of the isoforms of gasdermin-B did indeed poke holes to cause cell death—but other isoforms did not.

"'Previously, people didn't understand why studies contradicted each other. We show that only two of the isoforms of gasdermin-B cause pyroptosis, or cell death," says Ruan. Those two isoforms contain a specific protein segment that is absent in the other gasdermin-B isoforms, as shown by their cryogenic electron microscopy structure.

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"However, we don't yet know what these other isoforms are doing. It may be that the different isoforms of gasdermin-B play significant and distinctive roles depending on where they are in the body, and different cell types preferentially express different isoforms.

"'The protein structures that our team discovered have significant implications for drug development. Specifically, they can inform the design of small molecule drugs that modulate gasdermin-B activity," explains Ruan. "These drugs could potentially be used to treat a range of conditions, including cancer, inflammatory and autoimmune diseases, and infectious diseases by either suppressing or enhancing the immune response. Our findings thus hold promise for the development of novel therapies to address these pressing medical needs.'"

Comment: 3-D protein forms result in specific actions as this study shows. Why we differ from mice is an unanswerable question.