9p3y

Structural highlights

Function

GP_ANDV Forms homotetramers with glycoprotein C at the surface of the virion (By similarity). Attaches the virion to host cell receptors including integrin ITGAV/ITGB3 (By similarity). This attachment induces virion internalization possibly through clathrin-dependent endocytosis and dynamin-independent macropinocytosis (Probable). Mediates the assembly and budding of infectious virus particles through its interaction with the nucleocapsid protein and the viral genome (By similarity). May dysregulate normal immune and endothelial cell responses through an ITAM motif (By similarity). Translocates to mitochondria, binds to host TUFM and recruits MAP1LC3B (By similarity). These interactions induce mitochondrial autophagy and therefore destruction of host MAVS leading to inhibition of type I interferon (IFN) responses (By similarity). Concomitant breakdown of glycoprotein N is apparently prevented by the nucleoprotein that may inhibit Gn-stimulated autophagosome-lysosome fusion (By similarity). Interacts with the viral genomic RNA (By similarity). Inhibits the host RIG-I/TBK1 pathway by disrupting the formation of TBK1-TRAF3 complexes and downstream signaling responses required for IFN-beta transcription (PubMed:16973572, PubMed:24390324).[UniProtKB:P08668][UniProtKB:P27312]^{[1] [2]} Forms homotetramers with glycoprotein N at the surface of the virion. Attaches the virion to host cell receptors including integrin ITGAV/ITGB3. This attachment induces virion internalization predominantly through clathrin-dependent endocytosis (By similarity). Class II fusion protein that promotes fusion of viral membrane with host endosomal membrane after endocytosis of the virion (PubMed:27414047, PubMed:31180319).[UniProtKB:P08668]^{[3] [4]}

References

1. ↑ Alff PJ, Gavrilovskaya IN, Gorbunova E, Endriss K, Chong Y, Geimonen E, Sen N, Reich NC, Mackow ER. The pathogenic NY-1 hantavirus G1 cytoplasmic tail inhibits RIG-I TBK-1-directed interferon responses. J Virol. 2006 Oct;80(19):9676-86. PMID:16973572 doi:10.1128/JVI.00508-06
2. ↑ Matthys VS, Cimica V, Dalrymple NA, Glennon NB, Bianco C, Mackow ER. Hantavirus GnT elements mediate TRAF3 binding and inhibit RIG-I/TBK1-directed beta interferon transcription by blocking IRF3 phosphorylation. J Virol. 2014 Feb;88(4):2246-59. PMID:24390324 doi:10.1128/JVI.02647-13
3. ↑ Barriga GP, Villalón-Letelier F, Márquez CL, Bignon EA, Acuña R, Ross BH, Monasterio O, Mardones GA, Vidal SE, Tischler ND. Inhibition of the Hantavirus Fusion Process by Predicted Domain III and Stem Peptides from Glycoprotein Gc. PLoS Negl Trop Dis. 2016 Jul 14;10(7):e0004799. PMID:27414047 doi:10.1371/journal.pntd.0004799
4. ↑ Bignon EA, Albornoz A, Guardado-Calvo P, Rey FA, Tischler ND. Molecular organization and dynamics of the fusion protein Gc at the hantavirus surface. Elife. 2019 Jun 10;8:e46028. PMID:31180319 doi:10.7554/eLife.46028