6yrq
From Proteopedia
Crystal structure of the tetramerization domain of the glycoprotein Gn (Andes virus) at pH 4.6
Structural highlights
FunctionGP_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] Publication Abstract from PubMedHantaviruses are rodent-borne viruses causing serious zoonotic outbreaks worldwide for which no treatment is available. Hantavirus particles are pleomorphic and display a characteristic square surface lattice. The envelope glycoproteins Gn and Gc form heterodimers that further assemble into tetrameric spikes, the lattice building blocks. The glycoproteins, which are the sole targets of neutralizing antibodies, drive virus entry via receptor-mediated endocytosis and endosomal membrane fusion. Here we describe the high-resolution X-ray structures of the heterodimer of Gc and the Gn head and of the homotetrameric Gn base. Docking them into an 11.4-A-resolution cryoelectron tomography map of the hantavirus surface accounted for the complete extramembrane portion of the viral glycoprotein shell and allowed a detailed description of the surface organization of these pleomorphic virions. Our results, which further revealed a built-in mechanism controlling Gc membrane insertion for fusion, pave the way for immunogen design to protect against pathogenic hantaviruses. The Hantavirus Surface Glycoprotein Lattice and Its Fusion Control Mechanism.,Serris A, Stass R, Bignon EA, Muena NA, Manuguerra JC, Jangra RK, Li S, Chandran K, Tischler ND, Huiskonen JT, Rey FA, Guardado-Calvo P Cell. 2020 Sep 9. pii: S0092-8674(20)31064-3. doi: 10.1016/j.cell.2020.08.023. PMID:32937107[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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