title: SARS-CoV heptad repeat 2 is a trimer of parallel helices.
abstract: In severe acute respiratory syndrome coronavirus, the envelope heptad repeat 2 (HR2) plays a critical role in viral entry. Moreover, HR2 is both the target for novel antiviral therapies and, as an isolated peptide, presents a potential antiviral therapeutic. The structure of HR2, as determined by NMR spectroscopy in the presence of the co-solvent trifluoroethanol (TFE), is a trimer of parallel helices, whereas the structure of HR2, as determined by X-ray crystallography, is a tetramer of anti-parallel helices. In this work, we added a nitroxide spin label to the N-terminal region of HR2 and used paramagnetic relaxation enhancement to assess the orientation of the HR2 helices under different solution conditions. We find that the relaxation effects are consistent with an orientation corresponding to a trimer of parallel helices in both the presence and absence of TFE. This work suggests that the different orientation and oligomerization states observed by NMR and X-ray are due to the 11 additional residues present at the N-terminus of the NMR construct.
authors.affiliation: Department of Biochemistry & Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60607, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Celigoy
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ramirez
authors.forename: Michael
authors.initials: M
authors.lastname: Caffrey
mesh_terms: D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D045473:Severe acute respiratory syndrome-related coronavirus / Q000737:chemistry*; D045169:Severe Acute Respiratory Syndrome / Q000821:virology; D013113:Spin Labels; D014759:Viral Envelope Proteins / Q000737:chemistry*
chemical_list: D013113:Spin Labels; D014759:Viral Envelope Proteins