5JIF

Crystal structure of mouse hepatitis virus strain DVIM Hemagglutinin-Esterase

Summary for 5JIF

• Entry DOI: 10.2210/pdb5jif/pdb
• Descriptor: Hemagglutinin-esterase, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: hemagglutin, esterase, hepatitis virus, coronavirus, viral protein
• Biological source: Murine coronavirus (MHV-DVIM)
• Total number of polymer chains: 2
• Total formula weight: 93073.50

Authors

Zeng, Q.H.,Bakkers, M.J.G.,Feitsma, L.J.,de Groot, R.J.,Huizinga, E.G. (deposition date: 2016-04-22, release date: 2016-05-11, Last modification date: 2024-11-06)

Primary citation

Bakkers, M.J.,Zeng, Q.,Feitsma, L.J.,Hulswit, R.J.,Li, Z.,Westerbeke, A.,van Kuppeveld, F.J.,Boons, G.J.,Langereis, M.A.,Huizinga, E.G.,de Groot, R.J.
Coronavirus receptor switch explained from the stereochemistry of protein-carbohydrate interactions and a single mutation.
Proc.Natl.Acad.Sci.USA, 113:E3111-E3119, 2016

PubMed Abstract: Hemagglutinin-esterases (HEs) are bimodular envelope proteins of orthomyxoviruses, toroviruses, and coronaviruses with a carbohydrate-binding "lectin" domain appended to a receptor-destroying sialate-O-acetylesterase ("esterase"). In concert, these domains facilitate dynamic virion attachment to cell-surface sialoglycans. Most HEs (type I) target 9-O-acetylated sialic acids (9-O-Ac-Sias), but one group of coronaviruses switched to using 4-O-Ac-Sias instead (type II). This specificity shift required quasisynchronous adaptations in the Sia-binding sites of both lectin and esterase domains. Previously, a partially disordered crystal structure of a type II HE revealed how the shift in lectin ligand specificity was achieved. How the switch in esterase substrate specificity was realized remained unresolved, however. Here, we present a complete structure of a type II HE with a receptor analog in the catalytic site and identify the mutations underlying the 9-O- to 4-O-Ac-Sia substrate switch. We show that (i) common principles pertaining to the stereochemistry of protein-carbohydrate interactions were at the core of the transition in lectin ligand and esterase substrate specificity; (ii) in consequence, the switch in O-Ac-Sia specificity could be readily accomplished via convergent intramolecular coevolution with only modest architectural changes in lectin and esterase domains; and (iii) a single, inconspicuous Ala-to-Ser substitution in the catalytic site was key to the emergence of the type II HEs. Our findings provide fundamental insights into how proteins "see" sugars and how this affects protein and virus evolution.

PubMed: 27185912
DOI: 10.1073/pnas.1519881113

Experimental method

X-RAY DIFFRACTION (2 Å)