N-glycan structures, lectin domains, and glycoprotein?s fate in the secretory pathway

D'ALESSIO, C.

San Luis

Congreso; XLVIII Reunión Anual de la SAB; 2019

Sociedad Argentina de Biofísica

N-Glycanstructures, lectin domains, and glycoprotein?s fate in the secretory pathwayCeciliaD?Alessio1,2. 1 FundaciónInstituto Leloir and IIBBA-CONICET, 2 FCEN, UBA, Buenos Aires,Argentina.N-glycanstransferred to proteins are remodeled in the endoplasmic reticulum (ER) producingstructures that determine the fate of the glycoproteins within the secretorypathway. Glucosidase II (GII)is a key player in N-glycanprocessing as it removes the two inner glucose residues from the glycantransferred to proteins during N-glycosylationand the glucose residue added back to not yet properly folded proteins during thequality control of glycoprotein folding in the ER. GII is a heterodimer whosealpha subunit bears the catalytic site while its beta subunit enhancesdeglucosylation activity through its C-terminal Mannose-6-phosphate (M6P)receptor homology (MRH) domain. A family ofglycan receptors bearing MRH domains, including CD-MPR & CI-MPR (responsiblefor delivering acidic hydrolases with M6P signal to lysosomes), N-acetylglucosamine-1-phosphotransferase g subunit (responsible of generating the M6Psignal), OS-9(involved in the glycoprotein degradation pathway)and GII beta subunit recognize subtle differences in the N-glycan structures. Comparison oftheir structures showed a similar overall fold and identified conservedresidues critical for the structural integrity of the carbohydrate bindingpocket. Nonetheless, each one has its unique substrate specificity and itsbinding defines if the protein will continue in the folding process, will bedelivered to lysosomes or will be degraded in proteasomes. In the present work,we show the effects on GII activity of swapping its own GII beta MRH domain forthose MRH domains present in other lectins of the secretory pathway.