Protein cargo itself delays breakdown of GTP, according to PNAS study.

Scientists from the California Institute of Technology have uncovered properties of a pair of molecules that allow them to carry and deposit proteins to their correct locations within cells. They were studying the signal recognition particle (SRP) and the SRP receptor (SR), which are responsible for shuttling more than a third of all cellular proteins to their targets.

The investigators discovered that the binding of the protein cargo by SRP triggered the accelerated assembly of a molecular complex containing SRP, the cargo, and the SR protein. The SRP-SR complex then delivered the cargo to the cell membrane. Once there, the SRP-SR complex spontaneously changed its shape and deposited the cargo at the membrane.

The team also found that the presence of protein cargo delays the breakdown of guanosine triphosphate (GTP), from which the SRP and SR harvest the energy to form a complex with each other and to undergo all their molecular transformations. “GTP hydrolysis is like a timer that allows the SRP-SR complex to exist for a specified period of time before turning it off,” explains Shu-ou Shan, Ph.D., an assistant professor of chemistry at Caltech.

“By delaying this timer, the SRP-SR complex persists about 10 times longer than it would without the cargo. This ensures that there is sufficient time for the cargo to be properly delivered to the membrane.”

The researchers followed the movement of fluorescently tagged molecules to track the behavior of SRP and SR during the protein pick-up and delivery process.

The research could help scientists develop artificial delivery systems that help antibiotics target the SRP protein in bacteria. Blocking the bacterial SRP will kill bacteria, but since humans also have SRP proteins, Dr. Shan says it “will also likely affect the operation of cells in your body. Detailed mechanistic studies are required to figure out the difference between the mammalian and the bacteria SRP pathway and to find places to intervene where the bacterial SRP is uniquely susceptible.”

The paper appeared in the Proceedings of the National Academy of Sciences.

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