7k3g | pdb_00007k3g

SARS-CoV-2 Envelope Protein Transmembrane Domain: Pentameric Structure Determined by Solid-State NMR

spinqualitylabelsall models 7k3g, 10 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7k3g is a 5 chain structure with sequence from 2019-ncov. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Gene: E, 4 (2019-nCoV) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [VEMP_SARS2] Plays a central role in virus morphogenesis and assembly. Acts as a viroporin and self-assembles in host membranes forming pentameric protein-lipid pores that allow ion transport. Also plays a role in the induction of apoptosis.[HAMAP-Rule:MF_04204] Publication Abstract from PubMed Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing COVID-19 pandemic. Successful development of vaccines and antivirals against SARS-CoV-2 requires a comprehensive understanding of the essential proteins of the virus. The envelope (E) protein of SARS-CoV-2 assembles into a cation-selective channel that mediates virus budding, release, and host inflammation response. E blockage reduces virus pathogenicity while E deletion attenuates the virus. Here we report the 2.4 A structure and drug-binding site of E's transmembrane (TM) domain, determined using solid-state nuclear magnetic resonance (NMR) spectroscopy. In lipid bilayers that mimic the endoplasmic reticulum Golgi intermediate compartment (ERGIC) membrane, ETM forms a five-helix bundle surrounding a narrow central pore. The middle of the TM segment is distorted from the ideal a-helical geometry due to three regularly spaced phenylalanine residues, which stack within each helix and between neighboring helices. These aromatic interactions, together with interhelical Val and Leu interdigitation, cause a dehydrated pore compared to the viroporins of influenza and HIV viruses. Hexamethylene amiloride and amantadine bind shallowly to polar residues at the N-terminal lumen, while acidic pH affects the C-terminal conformation. These results indicate that SARS-CoV-2 E forms a structurally robust but bipartite channel whose N- and C-terminal halves can interact with drugs, ions and other viral and host proteins semi-independently. This structure establishes the atomic basis for designing E inhibitors as antiviral drugs against SARS-CoV-2. Structure and Drug Binding of the SARS-CoV-2 Envelope Protein in Phospholipid Bilayers.,Hong M, Mandala V, McKay M, Shcherbakov A, Dregni A, Kolocouris A Res Sq. 2020 Sep 24. doi: 10.21203/rs.3.rs-77124/v1. PMID:32995764 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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