4MOD
Structure of the MERS-CoV fusion core
Summary for 4MOD
| Entry DOI | 10.2210/pdb4mod/pdb |
| Related | 1WDF 1WNC |
| Descriptor | HR1 of S protein, LINKER, HR2 of S protein (2 entities in total) |
| Functional Keywords | mers-cov, viral envelope proteins, spike, trimer of hairpins, 6-helix bundle, membrane fusion, viral protein |
| Biological source | Human betacoronavirus 2c EMC/2012 (MERS-CoV) More |
| Total number of polymer chains | 2 |
| Total formula weight | 27805.08 |
| Authors | |
| Primary citation | Gao, J.,Lu, G.,Qi, J.,Li, Y.,Wu, Y.,Deng, Y.,Geng, H.,Li, H.,Wang, Q.,Xiao, H.,Tan, W.,Yan, J.,Gao, G.F. Structure of the fusion core and inhibition of fusion by a heptad repeat peptide derived from the S protein of Middle East respiratory syndrome coronavirus. J.Virol., 87:13134-13140, 2013 Cited by PubMed Abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) recently emerged as a severe worldwide public health concern. The virus is highly pathogenic, manifesting in infected patients with an approximately 50% fatality rate. It is known that the surface spike (S) proteins of coronaviruses mediate receptor recognition and membrane fusion, thereby playing an indispensable role in initiating infection. In this process, heptad repeats 1 and 2 (HR1 and HR2) of the S protein assemble into a complex called the fusion core, which represents a key membrane fusion architecture. To date, however, the MERS-CoV fusion core remains uncharacterized. In this study, we performed a series of biochemical and biophysical analyses characterizing the HR1/HR2 complexes of this novel virus. The HR sequences were variably truncated and then connected with a flexible amino acid linker. In each case, the recombinant protein automatically assembled into a trimer in solution, displaying a typical α-helical structure. One of these trimers was successfully crystallized, and its structure was solved at a resolution of 1.9 Å. A canonical 6-helix bundle, like those reported for other coronaviruses, was revealed, with three HR1 helices forming the central coiled-coil core and three HR2 chains surrounding the core in the HR1 side grooves. This demonstrates that MERS-CoV utilizes a mechanism similar to those of other class I enveloped viruses for membrane fusion. With this notion, we further identified an HR2-based peptide that could potently inhibit MERS-CoV fusion and entry by using a pseudotyped-virus system. These results lay the groundwork for future inhibitory peptidic drug design. PubMed: 24067982DOI: 10.1128/JVI.02433-13 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.901 Å) |
Structure validation
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