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TitleAtomic model of rabbit hemorrhagic disease virus by cryo-electron microscopy and crystallography.
Journal, issue, pagesPLoS Pathog, Vol. 9, Issue 1, Page e1003132, Year 2013
Publish dateJan 17, 2013
AuthorsXue Wang / Fengting Xu / Jiasen Liu / Bingquan Gao / Yanxin Liu / Yujia Zhai / Jun Ma / Kai Zhang / Timothy S Baker / Klaus Schulten / Dong Zheng / Hai Pang / Fei Sun /
PubMed AbstractRabbit hemorrhagic disease, first described in China in 1984, causes hemorrhagic necrosis of the liver. Its etiological agent, rabbit hemorrhagic disease virus (RHDV), belongs to the Lagovirus genus ...Rabbit hemorrhagic disease, first described in China in 1984, causes hemorrhagic necrosis of the liver. Its etiological agent, rabbit hemorrhagic disease virus (RHDV), belongs to the Lagovirus genus in the family Caliciviridae. The detailed molecular structure of any lagovirus capsid has yet to be determined. Here, we report a cryo-electron microscopic (cryoEM) reconstruction of wild-type RHDV at 6.5 Å resolution and the crystal structures of the shell (S) and protruding (P) domains of its major capsid protein, VP60, each at 2.0 Å resolution. From these data we built a complete atomic model of the RHDV capsid. VP60 has a conserved S domain and a specific P2 sub-domain that differs from those found in other caliciviruses. As seen in the shell portion of the RHDV cryoEM map, which was resolved to ~5.5 Å, the N-terminal arm domain of VP60 folds back onto its cognate S domain. Sequence alignments of VP60 from six groups of RHDV isolates revealed seven regions of high variation that could be mapped onto the surface of the P2 sub-domain and suggested three putative pockets might be responsible for binding to histo-blood group antigens. A flexible loop in one of these regions was shown to interact with rabbit tissue cells and contains an important epitope for anti-RHDV antibody production. Our study provides a reliable, pseudo-atomic model of a Lagovirus and suggests a new candidate for an efficient vaccine that can be used to protect rabbits from RHDV infection.
External linksPLoS Pathog / PubMed:23341770 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2 - 6.5 Å
Structure data

EMDB-5410: Cryo-electron microscopic reconstruction of wild rabbit hemorrhagic disease virus
PDB-3j1p: Atomic model of rabbit hemorrhagic disease virus
Method: EM (single particle) / Resolution: 6.5 Å

PDB-4egt:
Crystal structure of major capsid protein P domain from rabbit hemorrhagic disease virus
Method: X-RAY DIFFRACTION / Resolution: 2.0 Å

PDB-4ejr:
Crystal structure of major capsid protein S domain from rabbit hemorrhagic disease virus
Method: X-RAY DIFFRACTION / Resolution: 2.0 Å

Chemicals

ChemComp-HOH:
WATER / Water

Source
  • rabbit hemorrhagic disease virus
KeywordsVIRUS / icosahedral virus / calicivirus / lagovirus / VIRAL PROTEIN / capsid protein

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