Modulation of N-Glycosylation efficiency as mediated by translation speed. Bioinfomatic approach

LOPEZ MEDUS M; CARAMELO J

Córdoba

Congreso; 2do Congreso Argentino de Bioinformática y Biología Computacional; 2011

Sociedad Argentina de Bioinformática y Biología Computacional

Background: Oligosaccharyltransferase(OST) catalyzes the reaction between Glc3Man9GlcNAc2- PP-Dol and arginine residues in the NXS/T consensus regions of the proteins synthesized in the endoplasmic reticulum. However, not all of the molecules are modified, generating a heterogeneity in protein glycosylation. The N-Glycosylation is fundamentally cotranslational, therefore we speculate that the rate of protein translation can be decisive in this process, primarily affecting the efficiency of the OST. Since the use of different codons can affect the rate of synthesis, one can expect to find "slow" codons in a specific region downstream of the OSTs catalytic region. That is, when a region of the protein contains the sequence NXS/T, the synthesis should be slowed down, and a possible mechanism is the use of “slow” codons. On the other hand, much is known about the structural parameters of the ribosome, the translocon and the OST, from which one can estimate the distance between the OST and the ribosomal catalysis center as 200 Ȧ or its equivalent of 63 codons. Results: A bioinformatic search was conducted beginning with proteins annotated in Swiss-Prot containing N glycans,and including bibliographic data of said glycosylation. We searched for the mRNA corresponding to these proteins and found in the expected area, 63 residues downstream of N-glycosylation site, codons whose frequency of use is low, and finding a tendency in the expected region. Conclusions: This first approach, in a very basic manner, shows the plasticity of the information contained within the genes, which includes not only structural information but also can provide information necessary for the kinetic process of protein synthesis.