Gene for Acid Deglycosylating Enzyme Identified in Fish Embryos

Researchers at RIKEN have identified the gene responsible for an acid-active deglycosylating enzyme found in fish embryos. This enzyme, named ngly2, removes complex sugar molecules called glycans from proteins. Glycans are crucial for various biological processes, including protein quality control, cell differentiation, and immune responses.

Enzymes that remove glycans from proteins are known as peptide:N-glycanases (PNGases). While PNGases were initially discovered in bacteria and plants, they were later found in animals. Fish possess two types of PNGases: one active at acidic pH, found in embryos, and another active at neutral pH, present throughout the fish's life cycle.

Most research on PNGases has focused on the neutral-pH type, which is similar to the NGLY1 enzyme found in humans and other mammals. The acid-active PNGase, however, had received less attention because it is specific to fish embryos. Tadashi Suzuki and Akinobu Honda of the RIKEN Glycometabolic Biochemistry Laboratory sought to understand this overlooked enzyme.

The team successfully identified the gene encoding the acid PNGase, naming it ngly2. They also used cryo-electron microscopy to determine the enzyme's molecular structure. This structural information allowed them to design new biochemical experiments to test hypotheses about the enzyme's function.

Surprisingly, knocking out the ngly2 gene in zebrafish did not appear to significantly affect the embryos. Researchers hypothesize that this lack of observable effect might be due to zebrafish being freshwater fish. They suggest that knocking out ngly2 in saltwater fish could lead to more pronounced consequences.

This discovery has broader implications for marine species. The ngly2 gene is conserved across a wide range of aquatic organisms, including octopuses, ascidians, sea urchins, corals, and shellfish. This suggests that the gene may play a vital role in the adaptation of these organisms to aquatic environments.