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| | <StructureSection load='2ieq' size='340' side='right'caption='[[2ieq]], [[Resolution|resolution]] 1.75Å' scene=''> | | <StructureSection load='2ieq' size='340' side='right'caption='[[2ieq]], [[Resolution|resolution]] 1.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ieq]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Cvhnl Cvhnl]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IEQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IEQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ieq]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_coronavirus_NL63 Human coronavirus NL63]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IEQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IEQ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.747Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">S ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=277944 CVHNL])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ieq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ieq OCA], [https://pdbe.org/2ieq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ieq RCSB], [https://www.ebi.ac.uk/pdbsum/2ieq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ieq ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ieq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ieq OCA], [https://pdbe.org/2ieq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ieq RCSB], [https://www.ebi.ac.uk/pdbsum/2ieq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ieq ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/SPIKE_CVHNL SPIKE_CVHNL]] S1 region attaches the virion to the cell membrane by interacting with human ACE2, initiating the infection. Binding to the receptor probably induces conformational changes in the S glycoprotein unmasking the fusion peptide of S2 region and activating membranes fusion. S2 region belongs to the 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) regions 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).
| + | [https://www.uniprot.org/uniprot/SPIKE_CVHNL SPIKE_CVHNL] S1 region attaches the virion to the cell membrane by interacting with human ACE2, initiating the infection. Binding to the receptor probably induces conformational changes in the S glycoprotein unmasking the fusion peptide of S2 region and activating membranes fusion. S2 region belongs to the 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) regions 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). |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Cvhnl]] | + | [[Category: Human coronavirus NL63]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Liu, J]] | + | [[Category: Liu J]] |
| - | [[Category: Human coronavirus]]
| + | |
| - | [[Category: Membrane fusion]]
| + | |
| - | [[Category: S2]]
| + | |
| - | [[Category: Six-helix bundle]]
| + | |
| - | [[Category: Viral protein]]
| + | |
| - | [[Category: Virus entry]]
| + | |
| Structural highlights
Function
SPIKE_CVHNL S1 region attaches the virion to the cell membrane by interacting with human ACE2, initiating the infection. Binding to the receptor probably induces conformational changes in the S glycoprotein unmasking the fusion peptide of S2 region and activating membranes fusion. S2 region belongs to the 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) regions 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).
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Human coronavirus NL63 (HCoV-NL63) has recently been identified as a causative agent of acute respiratory tract illnesses in infants and young children. The HCoV-NL63 spike (S) protein mediates virion attachment to cells and subsequent fusion of the viral and cellular membranes. This viral entry process is a primary target for vaccine and drug development. HCoV-NL63 S is expressed as a single-chain glycoprotein and consists of an N-terminal receptor-binding domain (S1) and a C-terminal transmembrane fusion domain (S2). The latter contains two highly conserved heptad-repeat (HR) sequences that are each extended by 14 amino acids relative to those of the SARS coronavirus or the prototypic murine coronavirus, mouse hepatitis virus. Limited proteolysis studies of the HCoV-NL63 S2 fusion core identify an alpha-helical domain composed of a trimer of the HR segments N57 and C42. The crystal structure of this complex reveals three C42 helices entwined in an oblique and antiparallel manner around a central triple-stranded coiled coil formed by three N57 helices. The overall geometry comprises distinctive high-affinity conformations of interacting cross-sectional layers of the six helices. As a result, this structure is unusually stable, with an apparent melting temperature of 78 degrees C in the presence of the denaturant guanidine hydrochloride at 5 M concentration. The extended HR regions may therefore be required to prime the group 1 S glycoproteins for their fusion-activating conformational changes during viral entry. Our results provide an initial basis for understanding an intriguing interplay between the presence or absence of proteolytic maturation among the coronavirus groups and the membrane fusion activity of their S glycoproteins. This study also suggests a potential strategy for the development of improved HCoV-NL63 fusion inhibitors.
Core structure of S2 from the human coronavirus NL63 spike glycoprotein.,Zheng Q, Deng Y, Liu J, van der Hoek L, Berkhout B, Lu M Biochemistry. 2006 Dec 26;45(51):15205-15. Epub 2006 Dec 1. PMID:17176042[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zheng Q, Deng Y, Liu J, van der Hoek L, Berkhout B, Lu M. Core structure of S2 from the human coronavirus NL63 spike glycoprotein. Biochemistry. 2006 Dec 26;45(51):15205-15. Epub 2006 Dec 1. PMID:17176042 doi:10.1021/bi061686w
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