5w1k
JUNV GP1 CR1-10 Fab CR1-28 Fab complex
Structural highlights
FunctionGLYC_JUNIN 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 (By similarity). Glycoprotein G1 mediates virus attachment to host TFRC. This attachment induces virion internalization predominantly through clathrin-mediated endocytosis.[1] 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 PubMedWhile five arenaviruses cause human hemorrhagic fevers in the Western Hemisphere, only Junin virus (JUNV) has a vaccine. The GP1 subunit of their envelope glycoprotein binds transferrin receptor 1 (TfR1) using a surface that substantially varies in sequence among the viruses. As such, receptor-mimicking antibodies described to date are type-specific and lack the usual breadth associated with this mode of neutralization. Here we isolate, from the blood of a recipient of the live attenuated JUNV vaccine, two antibodies that cross-neutralize Machupo virus with varying efficiency. Structures of GP1-Fab complexes explain the basis for efficient cross-neutralization, which involves avoiding receptor mimicry and targeting a conserved epitope within the receptor-binding site (RBS). The viral RBS, despite its extensive sequence diversity, is therefore a target for cross-reactive antibodies with activity against New World arenaviruses of public health concern. Vaccine-elicited receptor-binding site antibodies neutralize two New World hemorrhagic fever arenaviruses.,Clark LE, Mahmutovic S, Raymond DD, Dilanyan T, Koma T, Manning JT, Shankar S, Levis SC, Briggiler AM, Enria DA, Wucherpfennig KW, Paessler S, Abraham J Nat Commun. 2018 May 14;9(1):1884. doi: 10.1038/s41467-018-04271-z. PMID:29760382[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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