5ft2
From Proteopedia
Sub-tomogram averaging of Lassa virus glycoprotein spike from virus- like particles at pH 5
Structural highlights
Function[GLYC_LASSJ] Stable signal peptide (SSP) is cleaved but is apparently retained as the third component of the GP complex. The SSP is required for efficient glycoprotein expression, post-translational cleavage of GP1 and GP2, glycoprotein transport to the cell plasma membrane, formation of infectious virus particles, and acid pH-dependent glycoprotein-mediated cell fusion. The GP complex interacts with host glycosylated LAMP1 to mediate efficient infection.[1] Glycoprotein G1 mediates virus attachment to host receptor alpha-dystroglycan DAG1. This attachment induces virion internalization predominantly through clathrin- and caveolin-independent endocytosis. Glycoprotein G2 is a class I viral fusion protein, that directs fusion of viral and host endosomal membranes, leading to delivery of the nucleocapsid into the cytoplasm. Membrane fusion is mediated by irreversable conformational changes induced upon acidification in the endosome (By similarity). Publication Abstract from PubMedLassa 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-A 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. Acidic pH-Induced Conformations and LAMP1 Binding of the Lassa Virus Glycoprotein Spike.,Li S, Sun Z, Pryce R, Parsy ML, Fehling SK, Schlie K, Siebert CA, Garten W, Bowden TA, Strecker T, Huiskonen JT PLoS Pathog. 2016 Feb 5;12(2):e1005418. doi: 10.1371/journal.ppat.1005418., eCollection 2016 Feb. PMID:26849049[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Lassj | Bowden, T A | Fehling, S K | Garten, W | Huiskonen, J T | Li, S | Parsy, M L | Pryce, R | Schlie, K | Siebert, C A | Strecker, T | Zhaoyang, S | Cell adhesion | Glycoprotein | Membrane fusion | Membrane protein | Receptor binding
