Characterization of the prefusion and transition states of severe acute respiratory syndrome coronavirus S2-HR2.
The envelope glycoproteins of the class I family, which include human immunodeficiency virus (HIV), influenza, and severe acute respiratory syndrome coronavirus (SARS-CoV), mediate viral entry by first binding to their cellular receptors and subsequently inducing fusion of the viral and cellular membranes. In the case of SARS-CoV, heptad repeat domains of the envelope glycoprotein, termed S2-HR1 and S2-HR2, are thought to undergo structural changes from a prefusion state, in which S2-HR1 and S2-HR2 do not interact, to a postfusion state in which S2-HR1 and S2-HR2 associate to form a six-helix bundle. In the present work, the structural and dynamic properties of S2-HR2 have been characterized. Evidence is presented for an equilibrium between a structured trimer thought to represent a prefusion state and an ensemble of unstructured monomers thought to represent a novel transition state. A model for viral entry is presented in which S2-HR2 is in a dynamic equilibrium between an ensemble of unstructured monomers in the transition state and a structured trimer in the prefusion state. Conversion from the prefusion state to the postfusion state requires passage through the transition state, a state that may give insight into the design of structure-based antagonists of SARS-CoV in particular, as well as other enveloped viruses in general.
McReynolds
Susanna
S
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60607, USA.
Jiang
Shaokai
S
Guo
Ying
Y
Celigoy
Jessica
J
Schar
Christine
C
Rong
Lijun
L
Caffrey
Michael
M
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D006023:Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D045473:Severe acute respiratory syndrome-related coronavirus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D053586:Virus Internalization
D006023:Glycoproteins; D014764:Viral Proteins