5omi
From Proteopedia
Crystal structure of GP2 from Lassa virus in a post fusion conformation
Structural highlights
FunctionGLYC_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 (LASV) is a notorious human pathogen in West Africa. Its class I trimeric spike complex displays a distinct architecture, and its cell entry mechanism involves unique attributes not shared by other related viruses. We determined the crystal structure of the GP2 fusion glycoprotein from the spike complex of LASV (GP2LASV) in its post-fusion conformation. GP2LASV adopts a canonical helical bundle configuration similarly to other viruses in its family. The core packing of GP2LASV, however, is more organized compared to GP2 from other viruses reducing the formation of internal hydrophobic cavities. We demonstrate a link between the formation of such unfavorable hydrophobic cavities and the efficiencies of membrane fusion and cell entry. Our study suggests that LASV has evolved a more efficient membrane fusogen compared to other viruses from its family by optimizing the post-fusion configuration of its GP2 module. Variations in Core Packing of GP2 from Old World Mammarenaviruses in their Post-Fusion Conformations Affect Membrane-Fusion Efficiencies.,Shulman A, Katz M, Cohen-Dvashi H, Greenblatt HM, Levy Y, Diskin R J Mol Biol. 2019 Apr 18. pii: S0022-2836(19)30206-2. doi:, 10.1016/j.jmb.2019.04.012. PMID:31004664[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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