4MBX

Structure of unliganded B-Lymphotropic Polyomavirus VP1

Summary for 4MBX

• Entry DOI: 10.2210/pdb4mbx/pdb
• Related: 4MBY 4MBZ
• Descriptor: Major Capsid Protein VP1, CALCIUM ION, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: jelly roll, polyomavirus, viral capsid (structural) protein, dna encapsidation, receptor binding, sialylated oligosaccharides, viral coat protein, viral protein
• Biological source: B-lymphotropic polyomavirus
• Total number of polymer chains: 10
• Total formula weight: 303327.21

Authors

Khan, Z.M.,Neu, U.,Schuch, B.,Stehle, T. (deposition date: 2013-08-21, release date: 2013-12-04, Last modification date: 2023-09-20)

Primary citation

Neu, U.,Khan, Z.M.,Schuch, B.,Palma, A.S.,Liu, Y.,Pawlita, M.,Feizi, T.,Stehle, T.
Structures of B-Lymphotropic Polyomavirus VP1 in Complex with Oligosaccharide Ligands.
Plos Pathog., 9:e1003714-e1003714, 2013

PubMed Abstract: B-Lymphotropic Polyomavirus (LPyV) serves as a paradigm of virus receptor binding and tropism, and is the closest relative of the recently discovered Human Polyomavirus 9 (HPyV9). LPyV infection depends on sialic acid on host cells, but the molecular interactions underlying LPyV-receptor binding were unknown. We find by glycan array screening that LPyV specifically recognizes a linear carbohydrate motif that contains α2,3-linked sialic acid. High-resolution crystal structures of the LPyV capsid protein VP1 alone and in complex with the trisaccharide ligands 3'-sialyllactose and 3'-sialyl-N-acetyl-lactosamine (3SL and 3SLN, respectively) show essentially identical interactions. Most contacts are contributed by the sialic acid moiety, which is almost entirely buried in a narrow, preformed cleft at the outer surface of the capsid. The recessed nature of the binding site on VP1 and the nature of the observed glycan interactions differ from those of related polyomaviruses and most other sialic acid-binding viruses, which bind sialic acid in shallow, more exposed grooves. Despite their different modes for recognition, the sialic acid binding sites of LPyV and SV40 are half-conserved, hinting at an evolutionary strategy for diversification of binding sites. Our analysis provides a structural basis for the observed specificity of LPyV for linear glycan motifs terminating in α2,3-linked sialic acid, and links the different tropisms of known LPyV strains to the receptor binding site. It also serves as a useful template for understanding the ligand-binding properties and serological crossreactivity of HPyV9.

PubMed: 24204265
DOI: 10.1371/journal.ppat.1003714

Experimental method

X-RAY DIFFRACTION (1.92 Å)