Conformational states of the severe acute respiratory syndrome coronavirus spike protein ectodomain.
The severe acute respiratory syndrome coronavirus enters cells through the activities of a spike protein (S) which has receptor-binding (S1) and membrane fusion (S2) regions. We have characterized four sequential states of a purified recombinant S ectodomain (S-e) comprising S1 and the ectodomain of S2. They are S-e monomers, uncleaved S-e trimers, cleaved S-e trimers, and dissociated S1 monomers and S2 trimer rosettes. Lowered pH induces an irreversible transition from flexible, L-shaped S-e monomers to clove-shaped trimers. Protease cleavage of the trimer occurs at the S1-S2 boundary; an ensuing S1 dissociation leads to a major rearrangement of the trimeric S2 and to formation of rosettes likely to represent clusters of elongated, postfusion trimers of S2 associated through their fusion peptides. The states and transitions of S suggest conformational changes that mediate viral entry into cells.
Li
Fang
F
Laboratory of Molecular Medicine, Children's Hospital, 320 Longwood Ave., Boston, MA 02115, USA.
Berardi
Marcelo
M
Li
Wenhui
W
Farzan
Michael
M
Dormitzer
Philip R
PR
Harrison
Stephen C
SC
D000085962:Angiotensin-Converting Enzyme 2; D003432:Cross-Linking Reagents / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D008854:Microscopy, Electron; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D007703:Peptidyl-Dipeptidase A / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D011485:Protein Binding; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D045473:Severe acute respiratory syndrome-related coronavirus / Q000502:physiology; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure
D003432:Cross-Linking Reagents; D008562:Membrane Glycoproteins; D046912:Multiprotein Complexes; D011991:Receptors, Virus; D011994:Recombinant Proteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; D007703:Peptidyl-Dipeptidase A; D000085962:Angiotensin-Converting Enzyme 2