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.