Cryo-EM structures of human oligosaccharyltransferase complexes OST-A and OST-B
Oligosaccharyltransferase (OST) is an integral membrane protein complex that catalyzes protein N-glycosylation in the endoplasmic reticulum. A recent “Science” paper by the Locher group describes the structure of human OST-A and OST-B complexes, providing the molecular basis of their distinct functions.
N- glycans play an essential role in protein folding, trafficking, and function. In mammals, two different OST complexes catalyze N-glycosylation in a co-translational or post-translational manner. They share six subunits but carry different catalytic subunits (STT3A or STT3B), which at the same time interact with specific adaptor proteins (DC2 or MAGT1). Using single-particle cryo-EM, the Locher group determined high-resolution structures of the OST-A and OST-B human complexes.
In OST-A, which catalyzes co-translational glycosylation, specific interactions between STT3A and DC2, the adapter protein that binds to the translocation channel, were identified. In addition, the C-terminal domain of Ribophorin-I, a subunit shared by both complexes is forming a 4-helix bundle that interacts with translating ribosome in OST-A, but it is unfolded in OST-B. The presence of substrates bound to the OST-B complex allowed the visualization of the active site and the identification of important residues for substrate binding and catalysis.
Link to the publication in external page"Science".