Molecular determinants that regulate de efficiency of protein N-glycosylation

PAULA M COUTO; MARIA S LABANDA; CARLOS GUARDIA; RODRIGO CORTI BIELSA; CARLOS LABRIOLA ; JULIO CARAMELO

Mar del Plata.

Congreso; 51 Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2015

SAIB

N-glycosylation is one of the most frequent protein modifications in eukaryotes. Nearly one quarter of eukaryotic proteins are N-glycosylated as they enter the lumen of the endoplasmic reticulum through the SEC61 translocon. This modification is carried out by the oligosaccharyl transferase enzyme (OST), an oligomeric complex associated with the SEC61. OST transfer a high mannose glycan to the lateral chain of ASN residues within the context ASN-X-SER/THR (where X cannot be PRO). This consensus sequence is known as N-glycosylation sequon. N-glycans fulfill several biological roles. For example, they assist the protein folding pathway in the ER and they can participate in several molecular recognition events. The presence of an N-glycosylation sequon does not guarantee its full occupation by the OST. For this reason, a protein may present a mixture of partially occupied sequons, a phenomenon known as N-glycosylation macroheterogeneity. It is known that some sequons are poorly recognized by the OST, for instance those displaying acidic residues in the middle. Nevertheless, the molecular determinants for this behavior are largely unknown. Here we study how the protein biosynthesis dynamics modulate this complex process.