Structure Of Vesicle That Transports Cargo Around Cells Is Determined

It’s an iconic image seen in high school biology textbooks: Vesicles bud from organelles inside cells and then travel to other cellular compartments carrying proteins. These proteins are either ready to be deployed for cellular activities such as secretion or are returning to home base for repackaging.

Researchers in Germany are now reporting the first complete structure of the outer protein coating of one of these transport vesicles. The coating is responsible for helping vesicles bud off an organelle’s membrane, fill up with the right cargo, and then deliver it to the right place in the cell. Specifically, the team analyzed the coating called COP1 (coat protein 1), which covers vesicles that move cargo from the Golgi apparatus to another cellular organelle called the endoplasmic reticulum (Science 2015, DOI: 10.1126/science.aab1121).

The 100-nm-wide shell making up COP1 is about 25 nm thick, and it contains hundreds of repeating units of eight different kinds of proteins, explains John A. G. Briggs at the European Molecular Biology Laboratory in Heidelberg, Germany, who led the team. One reason getting a glimpse of COP1 was so challenging is that the protein coat’s basic structural unit doesn’t form a rigid geometric pattern. Instead, the units have multiple ways of interacting and thus organizing into a three-dimensional container. This makes COP1 appear heterogeneous, even though there is an underlying order to the arrangement of proteins in the coat, comments Scott M. Stagg at Florida State University, who wasn’t involved in the research.

“The real wow aspect of this paper was the tour de force of cryoelectron tomography and biochemistry used to determine the structure,” Stagg says. The team took 82 images of 1,265 vesicles to obtain the 13-Å-resolution structure, which can delineate the positions and shapes of the proteins that form the coat. Then the team confirmed the 3-D placement of protein components using cross-linking and mass spectrometry. “This complicated question couldn’t have been answered otherwise,” Stagg adds.