Cell complexity: stimulus causes protein signalling (Introduction)

by David Turell , Tuesday, May 08, 2018, 00:51 (2393 days ago) @ David Turell

This study unravels how cells respond to stimuli through a 'tail' on an protein molecule:

https://phys.org/news/2018-05-uncovering-hidden-protein-tail-cell.html

"..researchers have found a previously-unknown mechanism that puts the brakes on an important cell signaling process involving the G proteins found in most living organisms.

"The mechanism, dubbed a "tail," is part of a small protein known mostly for its role in attaching larger structures to the cell membrane. When researchers inactivated the tail, a signaling response that had previously taken 30 minutes to occur happened almost immediately - with an intensity four times greater than normal.

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"We have discovered the mechanism that regulates how quickly a pathway gets turned on by an external stimulus," said Matthew Torres, an associate professor in the School of Biological Sciences at the Georgia Institute of Technology. "By genetically altering the control mechanism underlying this process, we are able to modulate how much of a signal from outside the cell gets inside the cell and how quickly it gets through. It's all the more astonishing because this mechanism has been hiding in plain sight for decades."

"G proteins, also known as guanine nucleotide-binding proteins, are a family of molecules that operate as molecular switches inside cells. They transmit signals acquired from a variety of extracellular stimuli to the interior of a cell - through the membrane, which otherwise wouldn't allow communication.

"The tail found by Torres and Doctoral Candidate Shilpa Choudhury likely escaped attention because it is flexibly attached to the G protein gamma subunit of a closely-collaborating protein team known as G beta/gamma. Protein structures have generally been identified by X-ray crystallography techniques which cannot resolve structures that are in motion.

"Prior to their work, the G gamma subunit has been known primarily as the protein that connects the larger G beta subunit to the cell membrane. Without the work of SAPH-ire - an informatics program that maps PTM activity using machine learning - the role of the tail structure might not have been identified.

"In yeast, G beta/gamma subunits activate a signaling pathway in response to pheromones, a process which normally takes about 30 minutes after stimulation of a pheromone receptor at the cell membrane. Torres and Choudhury suspected that protein modifications, PTMs, were somehow causing the delay. Their computer program SAPH-ire - developed in the Torres lab and announced in 2015 - pointed the finger straight at the G gamma subunit.

"The program analyzes existing meta-data repositories of protein sequence and PTM activity to reveal "hotspots" of protein alteration. SAPH-ire was designed to accelerate the search for important regulatory targets on protein structures and to provide a better understanding of how proteins communicate with one another inside cells.

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"Beyond identifying the control mechanism for the pathway, the researchers also learned how it controls the ability of yeast to respond to pheromones in a "switch-like" manner that is either on or off versus an analog manner that is analogous to a volume knob on a stereo.

"While Torres and Choudhury made their discovery in yeast, they believe it will have broad implications because all organisms that have G proteins, including humans, have G gamma tails that are riddled with PTMs. "

Comment: These are biomechanical molecules that control the speed of reactions in an automatic fashion. Note the tail moves. It is the coordinated dance of these molecules working automatically that produces life.