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:
LOPEZ MEDUS, M ; GOMEZ, GE; COUTO, PM; LANDOLFO, L; CARAMELO, JJ
Lugar:
Paraná, Entre Ríos
Reunión:
Congreso; 3er Congreso Argentino de Bioinformática y Biología Computacional; 2012
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