3TB0

Crystal structure of Rhesus Rotavirus VP8* in complex with N-Glycolylneuraminic acid

Summary for 3TB0

• Entry DOI: 10.2210/pdb3tb0/pdb
• Related: 3TAY
• Descriptor: Outer capsid protein VP4, methyl 3,5-dideoxy-5-[(hydroxyacetyl)amino]-D-glycero-alpha-D-galacto-non-2-ulopyranosidonic acid, GLYCEROL, ... (5 entities in total)
• Functional Keywords: beta sandwich, lectin, sugar binding protein, viral protein, neu5gc
• Biological source: Rhesus rotavirus (RV-A)
• Cellular location: Outer capsid protein VP4: Virion. Outer capsid protein VP8*: Virion. Outer capsid protein VP5*: Virion: P12473
• Total number of polymer chains: 1
• Total formula weight: 18917.82

Authors

Yu, X.,Blanchard, H. (deposition date: 2011-08-04, release date: 2012-10-17, Last modification date: 2024-02-28)

Primary citation

Yu, X.,Dang, V.T.,Fleming, F.E.,von Itzstein, M.,Coulson, B.S.,Blanchard, H.
Structural Basis of Rotavirus Strain Preference toward N-Acetyl- or N-Glycolylneuraminic Acid-Containing Receptors.
J.Virol., 86:13456-13466, 2012

PubMed Abstract: The rotavirus spike protein domain VP8* is essential for recognition of cell surface carbohydrate receptors, notably those incorporating N-acylneuraminic acids (members of the sialic acid family). N-Acetylneuraminic acids occur naturally in both animals and humans, whereas N-glycolylneuraminic acids are acquired only through dietary uptake in normal human tissues. The preference of animal rotaviruses for these natural N-acylneuraminic acids has not been comprehensively established, and detailed structural information regarding the interactions of different rotaviruses with N-glycolylneuraminic acids is lacking. In this study, distinct specificities of VP8* for N-acetyl- and N-glycolylneuraminic acids were revealed using biophysical techniques. VP8* protein from the porcine rotavirus CRW-8 and the bovine rotavirus Nebraska calf diarrhea virus (NCDV) showed a preference for N-glycolyl- over N-acetylneuraminic acids, in contrast to results obtained with rhesus rotavirus (RRV). Crystallographic structures of VP8* from CRW-8 and RRV with bound methyl-N-glycolylneuraminide revealed the atomic details of their interactions. We examined the influence of amino acid type at position 157, which is proximal to the ligand's N-acetyl or N-glycolyl moiety and can mutate upon cell culture adaptation. A structure-based hypothesis derived from these results could account for rotavirus discrimination between the N-acylneuraminic acid forms. Infectivity blockade experiments demonstrated that the determined carbohydrate specificities of these VP8* domains directly correlate with those of the corresponding infectious virus. This includes an association between CRW-8 adaption to cell culture, decreased competition by N-glycolylneuraminic acid for CRW-8 infectivity, and a Pro157-to-Ser157 mutation in VP8* that reduces binding affinity for N-glycolylneuraminic acid.

PubMed: 23035213
DOI: 10.1128/JVI.06975-11

Experimental method

X-RAY DIFFRACTION (2 Å)