Biological complexity: known cell complexity increases (Introduction)

by David Turell , Tuesday, March 15, 2022, 15:34 (984 days ago) @ David Turell

More regulatory cell research:

https://phys.org/news/2022-03-two-part-triggers-key-regulatory-protein.html

"Signaling proteins known as G-protein-coupled receptors (GPCRs) are found in the membranes of cells, and they convert signals from outside a cell into responses within a cell. They are responsible for reacting to signals from hormones, neurotransmitters and sensory signals from the eyes, nose and mouth. The critical role they play in cell biology is highlighted by the fact that roughly half of all drugs on pharmacy shelves target GPCRs.

"There has been much research into how GPCRs activate their scaffolding partners, known as β-arrestins, by binding to them. For a long time, β-arrestins were thought to be activated only by the tail end of GPCRs. But now, Ichio Shimada and Yutaro Shiraishi at the RIKEN Center for Biosystems Dynamics Research and five collaborators have shown how activation of β-arrestin also involves engagement with the GPCR core.

"Using nuclear magnetic resonance spectroscopy, the researchers discovered that β-arrestins bound to the tail of an interacting GPCR are only partially activated—subsequent binding with the core region is needed to push the β-arrestins into full activation mode. This, in turn, triggers downstream signaling cascades involved in everything from sight and smell to immune regulation and neuronal communication.

"'We have demonstrated that β-arrestin activation by GPCR involves two phases," says Shimada. That two-part chain of events helps to stabilize β-arrestins in their fully engaged, activated conformation.

"With an eye to drug development, the researchers also detailed how a drug-like antibody fragment helped to shift the balance in structural conformations to promote more activation-inducing interactions between β-arrestins and GPCRs, even in the absence of core binding.

"That finding highlights a path forward for therapeutically biasing the signaling activities of β-arrestins. "Variants of the antibody may be good candidates to modulate the signal transduction mediated by the GPCR–arrestin complex," says Shiraishi."

Comment: because of the demonstrated automaticity, we can use it to manage therapeutic measures. Cells are designed to work automatically. They just look intelligent.