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Structure of Merkel cell polyomavirus capsid and interaction with its glycosaminoglycan attachment receptor

DOI: 10.1128/JVI.01664-19 DOI Help

Authors: Niklas J. Bayer (University of Tübingen) , Dovile Januliene (Max-Planck-Institute of Biophysics) , Georg Zocher (University of Tübingen) , Thilo Stehle (University of Tübingen) , Arne Moeller (Max-Planck-Institute of Biophysics) , Bärbel S. Blaum (University of Tübingen)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Virology

State: Published (Approved)
Published: July 2020
Diamond Proposal Number(s): 14602

Open Access Open Access

Abstract: Merkel cell polyomavirus (MCPyV) is a human double-stranded DNA tumor virus. MCPyV cell entry is unique among the polyomavirus family as it requires the engagement of two types of glycans, sialylated oligosaccharides and sulfated glycosaminoglycans (GAGs). Here, we present crystallographic and cryo-electron microscopic structures of the icosahedral MCPyV capsid and analysis of its glycan interactions via NMR spectroscopy. While sialic acid binding is specific for α2-3-linked sialic acid and mediated by the exposed apical loops of the major capsid protein VP1, a broad range of GAG oligosaccharides bind to recessed regions between VP1 capsomers. Individual VP1 capsomers are tethered to one another by an extensive disulfide network that differs in architecture from previously-described interactions for other PyVs. An unusual C-terminal extension in MCPyV VP1 projects from the recessed capsid regions. Mutagenesis experiments show that this extension is dispensable for receptor interaction.

Diamond Keywords: Viruses; Merkel Cell Carcinoma (MCC); Skin Cancer

Subject Areas: Biology and Bio-materials, Chemistry, Medicine

Instruments: I03-Macromolecular Crystallography

Other Facilities: X06DA at SLS

Added On: 05/08/2020 09:47

Journal of Virology-2020-Bayer-JVI.01664-19.full.pdf

Discipline Tags:

Pathogens Non-Communicable Diseases Health & Wellbeing Cancer Biochemistry Chemistry Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)