IIBBA   05544
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Glucosidase II Beta Subunit MRH Domain: more than meets the eye
Autor/es:
ORSI, R.; D'ALESSIO, C; PARODI, AJ; GALLO, GL
Lugar:
Villa General Belgrano, Córdoba
Reunión:
Congreso; 2nd Argentinean Symposyum on Glycobiology; 2016
Resumen:
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 endoplasmic reticulum. GII is aheterodimer whose alpha subunit bears the catalytic site while its beta subunitenhances deglucosylation activity through its C-terminal Mannose-6-phosphate(M6P) receptor homology (MRH) domain. A familyof glycan receptors bearing MRH domains, including CD-MPR & CI-MPR (responsiblefor delivering acidic hydrolases with M6P signal to lysosomes), N-acetylglucosamine-1-phosphotransferaseg subunit(responsible of generating the M6P signal), OS-9 (involved in the glycoproteindegradation pathway) and GII beta subunitrecognize subtle differences in the N-glycanstructures. Comparison of their structures showeda similar overall fold and identified conserved residues critical for thestructural integrity of the carbohydrate binding pocket. Nonetheless, each has itsunique substrate specificity. In the present work, we show the effects on GIIactivity of swapping the MRH domain of its GII beta subunit for those of thetwo MPRs, OS-9 and the phosphotransferase gamma subunit.