Pentameric viral ion channels: from structure to function

Figures & data

Figure 1 Sequence alignment and secondary structure prediction of representative CoV envelope proteins.

Notes: (A) Alignment of E proteins in representatives from α-CoV (TGEV), α-coronavirus (MHV and SARS-CoV), and γ-coronavirus (IBV). A conserved polar residue and Proline are indicated by an arrow and star, respectively; (B) secondary structure and TM domain prediction.
Abbreviations: CoV, coronavirus; TGEV, the porcine transmissible gastroenteritis virus; MHV, murine hepatitis virus; SARS-CoV, severe acute respiratory syndrome coronavirus; IBV, infectious bronchitis virus; TM, transmembrane.

Figure 2 NMR-based models of SARS-CoV E proteins.

Notes: (A) Pore radius in the pentameric bundle formed by the TM domain of SARS-CoV E, ETM (8–38), showing the residues lining the hydrophilic pore; (B) solution NMR structure of E (8–65) in SDS⁴⁸ and α-helical conformation near the conserved Pro residue at the C-terminal tail; (C) side and cytoplasmic view of a pentameric bundle of SARS-CoV E derived from A and B. Each monomer is colored differently and extramembrane intermonomeric contacts are indicated. (A) Adapted from Pervushin K, Tan E, Parthasarathy K, et al. Structure and inhibition of the SARS coronavirus envelope protein ion channel. PLoS Path. 2009;5(7):e1000511.¹⁹ (B) This research was originally published in The Journal of Biological Chemistry. Li Y, Surya W, Claudine S, Torres J. Structure of a conserved golgi complex-targeting signal in coronavirus envelope proteins. J Biol Chem. 2014;289(18):12535–12549. © the American Society for Biochemistry and Molecular Biology.⁴⁸
Abbreviations: NMR, nuclear magnetic resonance; SARS-CoV, severe acute respiratory syndrome coronavirus; TM, transmembrane; SDS, sodium dodecyl sulphate.

Figure 3 Sequences of hRSV SH protein and homologs in paramyxoviruses.

Notes: (A) Alignment of sequences of hRSV SH protein and homologs, showing the TM domain (pink) and the prevalence of C-terminal Histidine residues, with a 3–4 residue periodicity; (B) pore profile through the pentameric bundle of RSV SH protein; (C) overlay of the monomeric structure obtained in DHPC/DLPC bicelles (blue) and DPC micelles (red); some side chains are indicated for comparison of the two structures; (D) model for the pentameric bundle of SH protein where each monomer is colored differently. (B) and (C) This research was originally published in The Journal of Biological Chemistry. Gan SW, Tan E, Lin X, et al. The small hydrophobic protein of the human respiratory syncytial virus forms pentameric ion channels. J Biol Chem. 2012;287(29):24671–24689. © the American Society for Biochemistry and Molecular Biology.⁶⁹ (C) Copyright © American Society for Microbiology, Journal of Virology, 2014;88(20):11899–11914, 10.1128/JVI.00839-14.⁸⁴
Abbreviations: hRSV, human respiratory syncytial virus; SH, small hydrophobic; TM, transmembrane; RSV, respiratory syncytial virus; DPC, dodecylphosphocholine.

Figure 4 Binding sites of inhibitors in SARS-CoV E and SH proteins. (A) Superposition of TROSY-HSQC spectra of uniformly ¹⁵N-labeled SARS-CoV E in the absence (red) and presence (blue) of 0.4 mM HMA (shown above image A). Peaks that undergo significant shifts upon complex formation are highlighted; (B) residues showing larger and smaller shifts are represented in red and yellow, respectively; (C) same as (A) for uniformly ¹⁵N-labeled SH protein in the absence (red) and presence (blue) of 4.8 mM pyronin B (shown above image C). (D) Residues showing larger and smaller shifts are represented in red and yellow, respectively.

Notes: (A) This research was originally published in The Journal of Biological Chemistry. Li Y, Surya W, Claudine S, Torres J. Structure of a conserved golgi complex-targeting signal in coronavirus envelope proteins. J Biol Chem. 2014;289(18):12535–12549. © the American Society for Biochemistry and Molecular Biology.⁴⁸ (C) and (D) Copyright © American Society for Microbiology, Journal of Virology. 2014;88(20):11899–11914, 10.1128/JVI.00839-14.⁸⁴
Abbreviations: SARS-CoV, severe acute respiratory syndrome coronavirus; SH, small hydrophobic; HMA, hexamethylene amiloride; TROSY-HSQC, transverse relaxation-optimized spectroscopy-heteronuclear single quantum coherence.

Figure 5 Common features in SARS-CoV E and RSV SH channels.

Notes: Simplified representation of the channel structure in both viroporins, where a funnel shape has a larger opening at the cytoplasmic side, and ends with a membrane-bound cytoplasmic α-helix. Both channels have the narrower end lumenally oriented, where binding of inhibitors has been mapped, and which coincides with well-conserved regions.
Abbreviations: SARS-CoV, severe acute respiratory syndrome coronavirus; SH, small hydrophobic; RSV, respiratory syncytial virus.

Li Y, Surya W, Claudine S, Torres J. Structure of a conserved golgi complex-targeting signal in coronavirus envelope proteins. J Biol Chem. 2014;289(18):12535–12549.

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Pervushin K, Tan E, Parthasarathy K, et al. Structure and inhibition of the SARS coronavirus envelope protein ion channel. PLoS Path. 2009;5(7):e1000511.

 PubMed Web of Science ®Google Scholar

Gan SW, Tan E, Lin X, et al. The small hydrophobic protein of the human respiratory syncytial virus forms pentameric ion channels. J Biol Chem. 2012;287(29):24671–24689.

 PubMed Web of Science ®Google Scholar

Li Y, To J, Verdià-Baguena C, et al. Inhibition of the human respiratory syncytial virus small hydrophobic protein and Structural variations in a bicelle environment. J Virol. 2014;88(20):11899–11914.

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