Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017160 (gastroenteritis)
 11,398 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Caliciviridae comprise a new family of single-stranded RNA viruses. While human caliciviruses cause gastroenteritis, the animal caliciviruses cause a wide range of diseases. We have determined the three-dimensional structure of a primate calicivirus using electron cryomicroscopy and computer image-processing techniques. Calicivirus is one of the rare animal viruses whose capsid is made of a single structural protein. The three-dimensional structure of the virus is distinct from that of any other animal virus. However, there are several architectural similarities with plant viruses such as tomato bushy stunt virus and turnip crinkle virus. The calicivirions are 405 A in diameter and exhibit T = 3 icosahedral symmetry. The main features of the three-dimensional structure are the 32 large surface hollows, 50 A deep and 90 A wide, at the icosahedral 5-fold and 3-fold axes, and the 90 distinctive arch-like capsomeres surrounding these hollows at the local and strict 2-fold axes. Each capsomere is a dimer of the capsid protein. Despite noticeable differences, the three quasi-equivalent subunits show common structural features: the upper bilobed domain, the central stem domain, and the lower shell domain. The 2-fold related capsid proteins interact through the bilobed domains to form the top of the arch. The structural differences between the connectors of the stem and the shell domain among the three subunits suggest the presence of a hinge region that may facilitate the capsid protein to adapt to the three quasi-equivalent environments of the T = 3 icosahedral structure. The shell domains of the pentavalent and hexavalent capsid proteins associate to form a continuous shell between the radii of 115 and 150 A. A beta-barrel structure has been suggested for the shell domain. The mass density in the inner shell between the radius of 85 and 110 A may contain a portion of the capsid protein interacting with the RNA. The features between the 45 and 85 A radius are suggestive of ordered RNA.
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PMID:Three-dimensional structure of calicivirus. 802 8

Norwalk virus, a noncultivatable human calicivirus, is the major cause of epidemic gastroenteritis in humans. The first x-ray structure of a calicivirus capsid, which consists of 180 copies of a single protein, has been determined by phase extension from a low-resolution electron microscopy structure. The capsid protein has a protruding (P) domain connected by a flexible hinge to a shell (S) domain that has a classical eight-stranded beta-sandwich motif. The structure of the P domain is unlike that of any other viral protein with a subdomain exhibiting a fold similar to that of the second domain in the eukaryotic translation elongation factor-Tu. This subdomain, located at the exterior of the capsid, has the largest sequence variation among Norwalk-like human caliciviruses and is likely to contain the determinants of strain specificity and cell binding.
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PMID:X-ray crystallographic structure of the Norwalk virus capsid. 1051 71

Norovirus is the most important cause of nonbacterial acute gastroenteritis. We have shown previously that the isolated P domain containing the hinge forms a dimer and binds to histo-blood group antigen (HBGA) receptors with a low affinity (M. Tan, R. S. Hegde, and X. Jiang, J. Virol. 78:6233-6242, 2004). Here, we reported that the P domain of VA387 without the hinge forms a small particle with a significantly increased receptor binding affinity. An end-linked oligopeptide containing one or more cysteines promoted P-particle formation by forming intermolecular disulfide bridges. The binding sensitivity of the P particle to HBGAs was enhanced >700-fold compared to the P dimer, which was comparable to that of virus-like particles. The binding specificity of the P particle was further confirmed by strong binding to the Caco-2 cells, a human colon carcinoma cell line. This binding enhancement was observed in the P particles of both norovirus GI and GII strains. The P particle is estimated to contain 12 P dimers, in which the P2 subdomain builds up the outer layer, while the P1 subdomain forms the internal core. Taken together, our data indicate that the P domain is involved not only in dimerization but also in polymerization of the protein during the capsid assembling. The enhanced receptor binding of the P particle reflects the intrinsic feature of the viral capsid. The easy production of the P particle and its strong binding to HBGAs suggest that the P particle is useful in studying pathogenesis and morphogenesis of norovirus and candidates for antiviral or vaccine development.
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PMID:The p domain of norovirus capsid protein forms a subviral particle that binds to histo-blood group antigen receptors. 1625 37

Norovirus is the major cause of epidemic nonbacterial gastroenteritis worldwide. Lack of structural information on infection and replication mechanisms hampers the development of effective vaccines and remedies. Here, using cryo-electron microscopy, we show that the capsid structure of murine noroviruses changes in response to aqueous conditions. By twisting the flexible hinge connecting two domains, the protruding (P) domain reversibly rises off the shell (S) domain in solutions of higher pH, but rests on the S domain in solutions of lower pH. Metal ions help to stabilize the resting conformation in this process. Furthermore, in the resting conformation, the cellular receptor CD300lf is readily accessible, and thus infection efficiency is significantly enhanced. Two similar P domain conformations were also found simultaneously in the human norovirus GII.3 capsid, although the mechanism of the conformational change is not yet clear. These results provide new insights into the mechanisms of non-enveloped norovirus transmission that invades host cells, replicates, and sometimes escapes the hosts immune system, through dramatic environmental changes in the gastrointestinal tract.
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PMID:Dynamic rotation of the protruding domain enhances the infectivity of norovirus. 3261 92