5gyq | pdb_00005gyq
Putative receptor-binding domain of bat-derived coronavirus HKU9 spike protein
Structural highlights
Function[SPIKE_BCHK9] S1 region attaches the virion to the cell membrane by interacting with cell receptors, initiating the infection. S2 is a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes (By similarity). Publication Abstract from PubMedThe suggested bat-origin for Middle East respiratory syndrome coronavirus (MERS-CoV) has revitalized the studies on other bat-derived coronaviruses for the interspecies transmission potential. Bat coronavirus (BatCoV) HKU9 is an important betacoronavirus (betaCoV) that is phylogenetically affiliated to the same genus as MERS-CoV. The bat-surveillance data indicated that BatCoV HKU9 has been widely spreading and circulating in bats. This highlights the necessity of characterizing the virus for its potential of crossing species barriers. The receptor binding domain (RBD) of the coronavirus spike (S) recognizes host receptors to mediate virus entry and is therefore a key factor determining the viral tropism and transmission capacity. In this study, the putative S RBD of BatCoV HKU9 (HKU9-RBD), which is homologous to other betaCoV RBDs that have been structurally and functionally defined, was characterized via a series of biophysical and crystallographic methods. By surface plasmon resonance, we demonstrated that HKU9-RBD binds to neither the SARS-CoV receptor of ACE2 nor the MERS-CoV receptor of CD26. We further solved the atomic structure of HKU9-RBD, which is expectedly composed of a core and an external subdomain. The core subdomain fold resembles those of other betaCoV RBDs; whereas the external subdomain is structurally unique with a single helix, explaining the inertness of HKU9-RBD to react with either ACE2 or CD26. Via comparison of thus-far available RBD structures, we further proposed a homologous inter-subdomain binding mode in betaCoV RBDs that anchors the core subdomain to the external subdomain. The revealed RBD features would shed light on the betaCoV evolution route. Putative receptor-binding domain of bat-derived coronavirus HKU9 spike protein: evolution of betacoronavirus receptor binding motifs.,Huang C, Qi J, Lu GW, Wang Q, Yuan Y, Wu Y, Zhang Y, Yan J, Gao GF Biochemistry. 2016 Oct 3. PMID:27696819[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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