Mechanism of cooperative N-glycan processing by the multi-modular endoglycosidase EndoE

Bacteria produce a remarkably diverse range of glycoside hydrolases to metabolize glycans from the environment as a primary source of nutrients, and to promote the colonization and infection of a host. Here we focus on EndoE, a multi-modular glycoside hydrolase secreted by Enterococcus faecalis, one...

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Detalles Bibliográficos
Autores: García-Alija, Mikel, Du, Jonathan J., Ordóñez ,Izaskun, Diz-Vallenilla, Asier, Moraleda-Montoya, Alicia, Sultana, Nazneen, Huynh, Chau G., Li, Chao, Connor Donahue, Thomas, Wang, Lai-Xi, Trastoy, Beatriz, Sundberg, Eric J., Guerin, Marcelo E.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/377725
Acceso en línea:http://hdl.handle.net/10261/377725
Access Level:acceso abierto
Palabra clave:Bacterial structural biology
Enzyme mechanisms
Glycobiology
X-ray crystallography
Descripción
Sumario:Bacteria produce a remarkably diverse range of glycoside hydrolases to metabolize glycans from the environment as a primary source of nutrients, and to promote the colonization and infection of a host. Here we focus on EndoE, a multi-modular glycoside hydrolase secreted by Enterococcus faecalis, one of the leading causes of healthcare-associated infections. We provide X-ray crystal structures of EndoE, which show an architecture composed of four domains, including GH18 and GH20 glycoside hydrolases connected by two consecutive three α-helical bundles. We determine that the GH20 domain is an exo-β-1,2-N-acetylglucosaminidase, whereas the GH18 domain is an endo-β-1,4-N-acetylglucosaminidase that exclusively processes the central core of complex-type or high-mannose-type N-glycans. Both glycoside hydrolase domains act in a concerted manner to process diverse N-glycans on glycoproteins, including therapeutic IgG antibodies. EndoE combines two enzyme domains with distinct functions and glycan specificities to play a dual role in glycan metabolism and immune evasion.