IIBBA   05544
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Eukaryotic secretory pathway proteins avoid occluded N-glycosylation sequons
Autor/es:
LÓPEZ MEDUS M; GÓMEZ G; LANDOLFO L ; CARAMELO J J
Lugar:
Paraná
Reunión:
Congreso; III Congreso Argentino de Bioinformática y Biología Computacional; 2012
Institución organizadora:
A2B2C
Resumen:
N-glycosylation is one of the most abundant and drastic posttranslational modifications. About 25 % of eukaryotic proteins are N-glycosylated when they enter the secretory pathway. N-glycans are important for the conformational maturation of glycoproteins and fulfill vital roles in several molecular recognition processes. This modification takes place on the sidechain of Asn residues within the context Asn-X-Ser/Thr (N-glycosylation sequon), where X can not be Pro. Even though all known N-glycans are located on the protein surface, N-glycosylation takes place before any major protein folding event, when proteins display an extended conformation. For this reason, it is possible the occupation of sequons normally buried on the protein structure, which in turn would seriously impair their folding process. There are two scenarios to avoid this situation: (1) secretory pathway proteins avoid occluded N-glycosylation sequons or (2) occluded sequons are not occupied. To answer this, we classified the protein data bank based on whether proteins belong or not to the eukaryotic secretory pathway. Next, we analyzed the surface exposition of Asn residues within the sequon context using the MSMS program. We found that secretory pathway proteins avoid occluded N-glycosylation sequons. Compared with non-secretory pathway proteins, Asn-X-Thr and Asn-X-Ser sequons are 6 and 3 times less frequent in secretory pathway proteins, respectively. This strong bias is highly specific, since it is absent in any of the remaining Ans-X-Y combinations. To generalize this result, we analyze the solvent exposition of the first residue present in the 400 Y1-X-Y2 combinations. Interestingly, we found that only N-glycosylation sequons display such a strong disparity between secretory and non-secretory pathway proteins.