title: Acidic pH-Induced Conformations and LAMP1 Binding of the Lassa Virus Glycoprotein Spike.
abstract: Lassa virus is an enveloped, bi-segmented RNA virus and the most prevalent and fatal of all Old World arenaviruses. Virus entry into the host cell is mediated by a tripartite surface spike complex, which is composed of two viral glycoprotein subunits, GP1 and GP2, and the stable signal peptide. Of these, GP1 binds to cellular receptors and GP2 catalyzes fusion between the viral envelope and the host cell membrane during endocytosis. The molecular structure of the spike and conformational rearrangements induced by low pH, prior to fusion, remain poorly understood. Here, we analyzed the three-dimensional ultrastructure of Lassa virus using electron cryotomography. Sub-tomogram averaging yielded a structure of the glycoprotein spike at 14-Å resolution. The spikes are trimeric, cover the virion envelope, and connect to the underlying matrix. Structural changes to the spike, following acidification, support a viral entry mechanism dependent on binding to the lysosome-resident receptor LAMP1 and further dissociation of the membrane-distal GP1 subunits.
authors: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors: Sai
authors: S
authors: Li
authors: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors: Zhaoyang
authors: Z
authors: Sun
authors: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors: Rhys
authors: R
authors: Pryce
authors: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors: Marie-Laure
authors: ML
authors: Parsy
authors: Institute of Virology, Philipps Universität Marburg, Marburg, Germany.
authors: Sarah K
authors: SK
authors: Fehling
authors: Institute of Virology, Philipps Universität Marburg, Marburg, Germany.
authors: Katrin
authors: K
authors: Schlie
authors: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors: C Alistair
authors: CA
authors: Siebert
authors: Institute of Virology, Philipps Universität Marburg, Marburg, Germany.
authors: Wolfgang
authors: W
authors: Garten
authors: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors: Thomas A
authors: TA
authors: Bowden
authors: Institute of Virology, Philipps Universität Marburg, Marburg, Germany.
authors: Thomas
authors: T
authors: Strecker
authors: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors: Juha T
authors: JT
authors: Huiskonen
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007836:Lassa virus / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D051907:Lysosomal Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008968:Molecular Conformation; D046912:Multiprotein Complexes; D011485:Protein Binding; D021382:Protein Sorting Signals; D017434:Protein Structure, Tertiary; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism*; D014771:Virion; D053586:Virus Internalization; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D006023:Glycoproteins; D051907:Lysosomal Membrane Proteins; D046912:Multiprotein Complexes; D021382:Protein Sorting Signals; D014759:Viral Envelope Proteins; C489116:LAMP1 protein, human; D052118:Lysosomal-Associated Membrane Protein 1