Yale researchers have discovered that a critical function of each cell — passing proteins through a membrane — is performed as a duet, not a solo.
An article published in the current issue of Science and featured on the cover describes the structure involved in the process, which is the signal recognition particle (SRP), said Jennifer Doudna, professor of molecular biophysics and biochemistry.
The SRP is made up of a protein and an RNA molecule.
What is surprising, Doudna said, is that the SRP structure suggests a role for the RNA in direct recognition of the signal peptide.
“What we think happens is that the RNA and the protein in the SRP work together to recognize the signal peptide,” Doudna said. “Previously it’s been thought that the functions of the proteins and the RNA were separate. Here we are seeing an example of true molecular collusion.”
The signal peptide within the cell is a molecular zip code that identifies the proteins that have to go through a membrane. “This paper,” she said, “describes the molecular structure of the machine that reads the zip code, which is the SRP. It reads the zip code, binds to the protein, and then transports the protein to the membrane of the cell.”
Doudna said it is not clear why the SRP has an RNA molecule.
“When we look at evolution from the three major kingdoms of life — bacteria, eukaryotes, and archaea — all have SRP and the same RNA that is part of the SRP,” she said. “Our lab has been interested in the role of RNA molecules in a variety of different biological functions. This current structure describes what the SRP looks like.”
The SRP sample used in the Yale project was taken from E coli bacteria and represents what would be found in humans and other organisms because of the SRP’s high degree of evolutionary conservation.
“The next step is to test the hypotheses we now have about the role of RNA in the SRP,” Doudna said. “One way we’re doing that is to see if we can introduce the signal peptide into crystals we have of the SRP core. The other thing we would like to know is how this part of the SRP is regulated.”
Other Yale researchers who collaborated on the study are Robert Batey, Robert Rambo, Louise Lucast, and Brian Rha, all in the Department of Molecular Biophysics and Biochemistry.
