Crystal structure of the prefusion surface glycoprotein of the prototypic arenavirus LCMV.
Arenaviruses exist worldwide and can cause hemorrhagic fever and neurologic disease. A single glycoprotein expressed on the viral surface mediates entry into target cells. This glycoprotein, termed GPC, contains a membrane-associated signal peptide, a receptor-binding subunit termed GP1 and a fusion-mediating subunit termed GP2. Although GPC is a critical target of antibodies and vaccines, the structure of the metastable GP1-GP2 prefusion complex has remained elusive for all arenaviruses. Here we describe the crystal structure of the fully glycosylated prefusion GP1-GP2 complex of the prototypic arenavirus LCMV at 3.5 Å. This structure reveals the conformational changes that the arenavirus glycoprotein must undergo to cause fusion and illustrates the fusion regions and potential oligomeric states.
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA.
Kathryn M
KM
Hastie
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA.
Sébastien
S
Igonet
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA.
Brian M
BM
Sullivan
SOLEIL Synchrotron, Gif-sur-Yvette, France.
Pierre
P
Legrand
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA.
Michelle A
MA
Zandonatti
Department of Pediatrics, School of Medicine, Tulane University, New Orleans, LA, USA.
James E
JE
Robinson
Department of Microbiology and Immunology, Tulane University, New Orleans, LA, USA.
Robert F
RF
Garry
Département de Virologie, Unité de Virologie Structurale, Institut Pasteur, Paris, France.
Félix A
FA
Rey
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA.
Michael B
MB
Oldstone
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA.|Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA.
Erica Ollmann
EO
Saphire
D000818:Animals; D002460:Cell Line; D018360:Crystallography, X-Ray; D004330:Drosophila; D006031:Glycosylation; D006801:Humans; D008216:Lymphocytic Choriomeningitis / Q000378:metabolism / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000737:chemistry* / Q000502:physiology; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D055503:Protein Multimerization; D021382:Protein Sorting Signals; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism; D053586:Virus Internalization
D008562:Membrane Glycoproteins; D021382:Protein Sorting Signals; D021122:Protein Subunits; D014759:Viral Envelope Proteins