N-glycosylation Triggers a Dual Selection Pressure in Eukaryotic Secretory Proteins

Abstract 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....

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Máximo Lopez Medus, Gabriela E. Gomez, Lucía F. Zacchi, Paula M. Couto, Carlos A. Labriola, María S. Labanda, Rodrigo Corti Bielsa, Eugenia M. Clérico, Benjamin L. Schulz, Julio J. Caramelo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/acdc1970e25b4dc48e101af8943a54cb
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:acdc1970e25b4dc48e101af8943a54cb
record_format	dspace
spelling	oai:doaj.org-article:acdc1970e25b4dc48e101af8943a54cb2021-12-02T16:07:48ZN-glycosylation Triggers a Dual Selection Pressure in Eukaryotic Secretory Proteins10.1038/s41598-017-09173-62045-2322https://doaj.org/article/acdc1970e25b4dc48e101af8943a54cb2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09173-6https://doaj.org/toc/2045-2322Abstract 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.Máximo Lopez MedusGabriela E. GomezLucía F. ZacchiPaula M. CoutoCarlos A. LabriolaMaría S. LabandaRodrigo Corti BielsaEugenia M. CléricoBenjamin L. SchulzJulio J. CarameloNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Máximo Lopez Medus Gabriela E. Gomez Lucía F. Zacchi Paula M. Couto Carlos A. Labriola María S. Labanda Rodrigo Corti Bielsa Eugenia M. Clérico Benjamin L. Schulz Julio J. Caramelo N-glycosylation Triggers a Dual Selection Pressure in Eukaryotic Secretory Proteins
description	Abstract 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.
format	article
author	Máximo Lopez Medus Gabriela E. Gomez Lucía F. Zacchi Paula M. Couto Carlos A. Labriola María S. Labanda Rodrigo Corti Bielsa Eugenia M. Clérico Benjamin L. Schulz Julio J. Caramelo
author_facet	Máximo Lopez Medus Gabriela E. Gomez Lucía F. Zacchi Paula M. Couto Carlos A. Labriola María S. Labanda Rodrigo Corti Bielsa Eugenia M. Clérico Benjamin L. Schulz Julio J. Caramelo
author_sort	Máximo Lopez Medus
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
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/acdc1970e25b4dc48e101af8943a54cb
work_keys_str_mv	AT maximolopezmedus nglycosylationtriggersadualselectionpressureineukaryoticsecretoryproteins AT gabrielaegomez nglycosylationtriggersadualselectionpressureineukaryoticsecretoryproteins AT luciafzacchi nglycosylationtriggersadualselectionpressureineukaryoticsecretoryproteins AT paulamcouto nglycosylationtriggersadualselectionpressureineukaryoticsecretoryproteins AT carlosalabriola nglycosylationtriggersadualselectionpressureineukaryoticsecretoryproteins AT mariaslabanda nglycosylationtriggersadualselectionpressureineukaryoticsecretoryproteins AT rodrigocortibielsa nglycosylationtriggersadualselectionpressureineukaryoticsecretoryproteins AT eugeniamclerico nglycosylationtriggersadualselectionpressureineukaryoticsecretoryproteins AT benjaminlschulz nglycosylationtriggersadualselectionpressureineukaryoticsecretoryproteins AT juliojcaramelo nglycosylationtriggersadualselectionpressureineukaryoticsecretoryproteins
_version_	1718384736929316864

N-glycosylation Triggers a Dual Selection Pressure in Eukaryotic Secretory Proteins

Ejemplares similares