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

DOI: 10.1038/s41467-022-28722-w DOI Help

Authors: Mikel García-Alija (Cruces University Hospital; Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)) , Jonathan J. Du (Emory University School of Medicine) , Izaskun Ordóñez (Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)) , Asier Diz-Vallenilla (Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)) , Alicia Moraleda-Montoya (Cruces University Hospital; Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)) , Nazneen Sultana (Emory University School of Medicine) , Chau G. Huynh (Emory University School of Medicine) , Chao Li (University of Maryland) , Thomas Connor Donahue (University of Maryland) , Lai-Xi Wang (University of Maryland) , Beatriz Trastoy (Cruces University Hospital; Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA)) , Eric J. Sundberg (Emory University School of Medicine) , Marcelo E. Guerin (Cruces University Hospital; Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA))
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 13

State: Published (Approved)
Published: March 2022
Diamond Proposal Number(s): 20113

Open Access Open Access

Abstract: 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.

Journal Keywords: Bacterial structural biology; Enzyme mechanisms; Glycobiology; X-ray crystallography

Diamond Keywords: Enzymes; Bacteria

Subject Areas: Biology and Bio-materials


Instruments: B21-High Throughput SAXS , I24-Microfocus Macromolecular Crystallography

Other Facilities: BL13-XALOC at ALBA; X06DA at SLS; P11 at PETRA III

Added On: 08/03/2022 09:21

Discipline Tags:

Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Scattering Macromolecular Crystallography (MX) Small Angle X-ray Scattering (SAXS)