Study On The Binding Mechanism Of Norovirus And Tissue Antigen

Norovirus(NoV) causes epidemic acute gastroenteritis in humans,whereby histo-blood group antigens (HBGAs) play an important role in host susceptibility. Human norovirus (huNoV) has diverged into two major lineages (Gâ…  and Gâ…¡) selected by HBGAs.Both lineages further diverge into various sub-lineages (genotypes). Each of the two major genogroups (Gâ…  and Gâ…¡) of huNoVs recognizes a unique set of HBGAs through a distinct binding interface that is conserved within a genogroup, indicating a distinct evolutionary path for each genogroup. In this study, through X-ray crystallography of the P domain of a GII.21 huNoV (OIF), we found that it does not share the conserved Gâ…¡ binding interface, revealing a new evolution lineage with a distinct HBGA binding interface. Sequence alignment showed that the major residues contributing to the new HBGA binding interface are conserved among most members of the GII.21, as well as a closely related GIL 13 genotype. In addition, we found that glycerol inhibits OIF binding to HBGAs, potentially allowing production of cheap antivirals againsthuNoVs.Taken together, our results reveal a new evolutionary lineage of NoVs selected by HBGAs, our finding raises an alert on future emergence of new lineages via developing new receptor binding interfaces, as well as further divergence of this new lineage into more sub-lineages recognizing different HBGAs, whichmay impact future epidemiology and strategies for disease control and prevention against huNoVs.G protein-coupled receptors (GPCRs) are the largest class of receptors in the human genome and are the most commonly trageted membrane protein class for medicinal therapeutics. We screened out neurokinin 3(NK3) receptor from 20 targets. NK3 receptor is one kind of tachykinin receptors, and it has been evaluated as a potential target for treatment of schizophrenia. We can get a stable variants of NK3R by trunction, inserting fusion partners, mutations and using ligands. So far our work establishes the foundation for the following study of cryctal structure.