N-glycosylation Triggers a Dual Selection Pressure in Eukaryotic Secretory Proteins
Nearly one third of the eukaryotic proteome traverses the secretory pathway and most of these proteins are N-glycosylated in the lumen of the endoplasmic reticulum. N-glycans fulfill multiple structural and biological functions, and are crucial for productive folding of many glycoproteins. N-glycosy...
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2017
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_20452322_v7_n1_p_Medus http://hdl.handle.net/20.500.12110/paper_20452322_v7_n1_p_Medus |
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paper:paper_20452322_v7_n1_p_Medus2023-06-08T16:33:30Z N-glycosylation Triggers a Dual Selection Pressure in Eukaryotic Secretory Proteins glycoprotein membrane protein protein binding animal biology chemistry Chlorocebus aethiops CV-1 cell line endoplasmic reticulum eukaryotic cell genetic disorder genetic selection genetics glycosylation human metabolism molecular model procedures protein conformation Animals Cercopithecus aethiops Computational Biology COS Cells Endoplasmic Reticulum Eukaryotic Cells Genetic Diseases, Inborn Glycoproteins Glycosylation Humans Membrane Proteins Models, Molecular Protein Binding Protein Conformation Selection, Genetic Nearly one third of the eukaryotic proteome traverses the secretory pathway and most of these proteins are N-glycosylated in the lumen of the endoplasmic reticulum. N-glycans fulfill multiple structural and biological functions, and are crucial for productive folding of many glycoproteins. N-glycosylation involves the attachment of an oligosaccharide to selected asparagine residues in the sequence N-X-S/T (X P), a motif known as an N-glycosylation'sequon'. Mutations that create novel sequons can cause disease due to the destabilizing effect of a bulky N-glycan. Thus, an analogous process must have occurred during evolution, whenever ancestrally cytosolic proteins were recruited to the secretory pathway. Here, we show that during evolution N-glycosylation triggered a dual selection pressure on secretory pathway proteins: while sequons were positively selected in solvent exposed regions, they were almost completely eliminated from buried sites. This process is one of the sharpest evolutionary signatures of secretory pathway proteins, and was therefore critical for the evolution of an efficient secretory pathway. © 2017 The Author(s). 2017 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_20452322_v7_n1_p_Medus http://hdl.handle.net/20.500.12110/paper_20452322_v7_n1_p_Medus |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
glycoprotein membrane protein protein binding animal biology chemistry Chlorocebus aethiops CV-1 cell line endoplasmic reticulum eukaryotic cell genetic disorder genetic selection genetics glycosylation human metabolism molecular model procedures protein conformation Animals Cercopithecus aethiops Computational Biology COS Cells Endoplasmic Reticulum Eukaryotic Cells Genetic Diseases, Inborn Glycoproteins Glycosylation Humans Membrane Proteins Models, Molecular Protein Binding Protein Conformation Selection, Genetic |
| spellingShingle |
glycoprotein membrane protein protein binding animal biology chemistry Chlorocebus aethiops CV-1 cell line endoplasmic reticulum eukaryotic cell genetic disorder genetic selection genetics glycosylation human metabolism molecular model procedures protein conformation Animals Cercopithecus aethiops Computational Biology COS Cells Endoplasmic Reticulum Eukaryotic Cells Genetic Diseases, Inborn Glycoproteins Glycosylation Humans Membrane Proteins Models, Molecular Protein Binding Protein Conformation Selection, Genetic N-glycosylation Triggers a Dual Selection Pressure in Eukaryotic Secretory Proteins |
| topic_facet |
glycoprotein membrane protein protein binding animal biology chemistry Chlorocebus aethiops CV-1 cell line endoplasmic reticulum eukaryotic cell genetic disorder genetic selection genetics glycosylation human metabolism molecular model procedures protein conformation Animals Cercopithecus aethiops Computational Biology COS Cells Endoplasmic Reticulum Eukaryotic Cells Genetic Diseases, Inborn Glycoproteins Glycosylation Humans Membrane Proteins Models, Molecular Protein Binding Protein Conformation Selection, Genetic |
| description |
Nearly one third of the eukaryotic proteome traverses the secretory pathway and most of these proteins are N-glycosylated in the lumen of the endoplasmic reticulum. N-glycans fulfill multiple structural and biological functions, and are crucial for productive folding of many glycoproteins. N-glycosylation involves the attachment of an oligosaccharide to selected asparagine residues in the sequence N-X-S/T (X P), a motif known as an N-glycosylation'sequon'. Mutations that create novel sequons can cause disease due to the destabilizing effect of a bulky N-glycan. Thus, an analogous process must have occurred during evolution, whenever ancestrally cytosolic proteins were recruited to the secretory pathway. Here, we show that during evolution N-glycosylation triggered a dual selection pressure on secretory pathway proteins: while sequons were positively selected in solvent exposed regions, they were almost completely eliminated from buried sites. This process is one of the sharpest evolutionary signatures of secretory pathway proteins, and was therefore critical for the evolution of an efficient secretory pathway. © 2017 The Author(s). |
| title |
N-glycosylation Triggers a Dual Selection Pressure in Eukaryotic Secretory Proteins |
| title_short |
N-glycosylation Triggers a Dual Selection Pressure in Eukaryotic Secretory Proteins |
| title_full |
N-glycosylation Triggers a Dual Selection Pressure in Eukaryotic Secretory Proteins |
| title_fullStr |
N-glycosylation Triggers a Dual Selection Pressure in Eukaryotic Secretory Proteins |
| title_full_unstemmed |
N-glycosylation Triggers a Dual Selection Pressure in Eukaryotic Secretory Proteins |
| title_sort |
n-glycosylation triggers a dual selection pressure in eukaryotic secretory proteins |
| publishDate |
2017 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_20452322_v7_n1_p_Medus http://hdl.handle.net/20.500.12110/paper_20452322_v7_n1_p_Medus |
| _version_ |
1768546606093697024 |