4X1Z

Crystal structure of RHDVb P domain in complex with H type 2

Summary for 4X1Z

• Entry DOI: 10.2210/pdb4x1z/pdb
• Related PRD ID: PRD_900125
• Descriptor: VP1, alpha-L-fucopyranose-(1-2)-beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-alpha-D-glucopyranose, SODIUM ION, ... (4 entities in total)
• Functional Keywords: major capsid protein, capsid spike, protruding domain, hbga binding, viral protein
• Biological source: Rabbit hemorrhagic disease virus (RHDV)
• Total number of polymer chains: 2
• Total formula weight: 69840.41

Authors

Leuthold, M.M.,Hansman, G.S. (deposition date: 2014-11-25, release date: 2015-01-14, Last modification date: 2024-01-10)

Primary citation

Leuthold, M.M.,Dalton, K.P.,Hansman, G.S.
Structural analysis of a rabbit hemorrhagic disease virus binding to histo-blood group antigens.
J.Virol., 89:2378-2387, 2015

PubMed Abstract: Rabbit hemorrhagic disease virus (RHDV) is a member of the Caliciviridae family (Lagovirus genus). RHDV is highly contagious and attaches to epithelial cells in the digestive or respiratory tract, leading to massive lesions with high mortality rates. A new variant of RHDV (termed RHDVb) recently has emerged, and previously vaccinated rabbits appear to have little protection against this new strain. Similar to human norovirus (Caliciviridae, Norovirus genus), RHDV binds histo-blood group antigens (HBGAs), and this is thought to be important for infection. Here, we report the HBGA binding site on the RHDVb capsid-protruding domain (P domain) using X-ray crystallography. The HBGA binding pocket was located in a negatively charged patch on the side of the P domain and at a dimeric interface. Residues from both monomers contributed to the HBGA binding and involved a network of direct hydrogen bonds and water-mediated interactions. An amino acid sequence alignment of different RHDV strains indicated that the residues directly interacting with the ABH-fucose of the HBGAs (Asp472, Asn474, and Ser479) were highly conserved. This result suggested that different RHDV strains also could bind HBGAs at the equivalent pocket. Moreover, several HBGA binding characteristics between RHDVb and human genogroup II norovirus were similar, which indicated a possible convergent evolution of HBGA binding interactions. Further structural studies with other RHDV strains are needed in order to better understand the HBGA binding mechanisms among the diverse RHDV strains.

PubMed: 25505081
DOI: 10.1128/JVI.02832-14

Experimental method

X-RAY DIFFRACTION (1.36 Å)