Glycoprotein Folding

PAULA MONSERRAT COUTO; CARAMELO , JJ

Molecular Nutrition: Carbohydrates

Academic Press

Lugar: Londres; Año: 2019; p. 60 - 71

Approximately one-third of eukaryotic proteins belong to the secretory pathway. They enterthe endoplasmic reticulum (ER) either co- or posttranslationally through the Sec61 αβγtranslocon complex. In the ER, these proteins are chemically modified and acquire their nativetertiary and quaternary structures. The most common modifications are the attachmentof N-glycans and the formation of disulfide bridges. Nearly 80% of secretory pathway proteinsare N-glycosylated at the lateral chain of asparagine residues displayed in the contextAsn-X-Ser/Thr (X cannot be proline), a motif known as N-glycosylation sequon. In somecases, other consensus sequences such as Asn-X-Cys/Gly/Val can be employed. N-glycansfulfill several biological and structural roles. They are bulky and hydrophilic moieties thatcan be considered as covalently attached ?chemical chaperones,? preventing nonspecific contactsand modulating the stability of glycoproteins (Helenius and Aebi, 2004). N-glycans alsofavor the acquisition of secondary structural elements such as turns and provide protectiontoward proteolysis. On the other hand, the great diversity of mature N-glycans plays a centralrole in numerous molecular recognition events, modulating process such as migration,differentiation, and proliferation. N-glycans present transiently in the ER are exploited asa platform that encodes information about the folding status and age of glycoproteins, thusallowing the action of specialized folding machinery.