Design and Structure of an Engineered Disulfide-Stabilized Influenza Virus Hemagglutinin Trimer.
We engineered a disulfide-stabilized influenza virus hemagglutinin (HA) trimer, termed HA3-SS, by introducing cysteine residues into the HA stem to covalently bridge the three protomers. HA3-SS has increased thermostability compared to wild-type HA, and binding of head- and stem-targeted antibodies (Abs) is preserved; only minor structural changes are found in the vicinity of the additional disulfide. This platform has been applied to H1 and H3 HAs and provides prospects for design of intact, stabilized influenza virus HA immunogens.
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA.
Peter S
PS
Lee
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.
Xueyong
X
Zhu
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.
Wenli
W
Yu
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA wilson@scripps.edu.
Ian A
IA
Wilson
D000914:Antibodies, Viral / Q000276:immunology*; D000956:Antigens, Viral / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D004220:Disulfides; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D006801:Humans; D009975:Orthomyxoviridae / Q000235:genetics / Q000276:immunology*; D011485:Protein Binding; D055550:Protein Stability; D013696:Temperature
D000914:Antibodies, Viral; D000956:Antigens, Viral; D004220:Disulfides; D019267:Hemagglutinin Glycoproteins, Influenza Virus