SH pentamer transports K+

Stable Identifier
R-HSA-9837835
Type
Reaction [transition]
Species
Homo sapiens
Related Species
Human respiratory syncytial virus A
Compartment
trans-Golgi network membrane, Golgi lumen, cytosol
ReviewStatus
5/5
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SH pentamer transports K+
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The small hydrophobic (SH) protein of respiratory syncytial virus (RSV) possesses viroporin properties, forming pentameric ion channels within lipid-raft structures in the Golgi membrane of infected cells (Gan SW et al. 2008, 2012; Triantafilou K et al. 2013; Li Y et al. 2014). The ion channel activity of viral SH results in imbalance of intracellular ions, thus contributing to the activation of NLRP3 inflammasome (Triantafilou K et al. 2013). RSV lacking SH fails to induce NLRP3-mediated caspase-1 activation and IL-1β secretion in human lung epithelial cells (Triantafilou K et al. 2013). Blocking the ion channel activity of SH with a small molecule called pyronin B reduces RSV virus production in monkey epithelial kidney Vero cells suggesting that targeting ion channel activity of SH could be a potential anti-RSV strategy (Li Y et al. 2014). Biochemical and spectroscopic analysis have shown that SH is a transmembrane protein with a single hydrophobic region spanning the membrane and a cytosolic tail at the carboxyl terminus (Carter Sd et al. 2010; Gan SW et al. 2012; Li Y et al. 2014). It is composed of α-helices in the transmembrane domains and a small α-helix at the C-terminus. SH has been shown to form a pentameric arrangement with a central pore in the transmembrane domain (Carter Sd et al. 2010; Gan SW et al. 2012; Li Y et al. 2014). Molecular modeling studies support the idea that SH functions as a viroporin forming pores that increase membrane permeability to ions and small molecules (Carter Sd et al. 2010; Li Y et al. 2014; Araujo GC et al. 2016). Besides inducing NLRP3 inflammasome formation, SH has been implicated in inhibiting apoptotic cell death potentially through its interaction with B cell associated protein 31 (BAP31) (Li Y et al. 2015). Both processes contribute to the pathogenesis of RSV.

This Reactome event shows RSV SH-mediated transport of potassium (K+) ions from the Golgi lumen to the cytosol.

Literature References
PubMed ID Title Journal Year
27817112 Structure and functional dynamics characterization of the ion channel of the human respiratory syncytial virus (hRSV) small hydrophobic protein (SH) transmembrane domain by combining molecular dynamics with excited normal modes

Souza, FP, Silva, RH, Araujo, AS, de Oliveira, RJ, Scott, LP, Araujo, GC

J Mol Model 2016
25100835 Inhibition of the human respiratory syncytial virus small hydrophobic protein and structural variations in a bicelle environment

Li, Y, Paulmichl, M, Liu, DX, Dossena, S, Aguilella, VM, Verdiá-Báguena, C, Surya, W, Torres, J, Huang, M, To, J

J Virol 2014
23229815 Human respiratory syncytial virus viroporin SH: a viral recognition pathway used by the host to signal inflammasome activation

Kar, S, Triantafilou, M, Triantafilou, K, Vakakis, E, Kotecha, S

Thorax 2013
20471980 Direct visualization of the small hydrophobic protein of human respiratory syncytial virus reveals the structural basis for membrane permeability

Foster, TL, Gorny, P, Barr, JN, Griffin, S, Atkins, E, Ranson, NA, Verow, M, Harris, M, Dent, KC, Carter, SD, Hiscox, JA

FEBS Lett 2010
22621926 The small hydrophobic protein of the human respiratory syncytial virus forms pentameric ion channels

Yeo, CY, Gan, SW, Pervushin, K, Soong, TW, Yu, D, Soon, CH, Wang, J, Vararattanavech, A, Tan, GM, Torres, J, Lin, X, Tan, E

J Biol Chem 2012
18369195 Structure and ion channel activity of the human respiratory syncytial virus (hRSV) small hydrophobic protein transmembrane domain

Gong, X, Gan, SW, Torres, J, Lin, X, Ng, L

Protein Sci 2008
Participants
Input
Output
Participates
as an event of
Catalyst Activity

monoatomic cation channel activity of p-SH pentamer [trans-Golgi network membrane]

Physical Entity
p-SH pentamer [trans-Golgi network membrane] (Human respiratory syncytial virus A)
Activity
monoatomic cation channel activity (GO:0005261)
Disease
Cross References
Rhea
Authored
Shamovsky, V  (2023-06-19)
Reviewed
Bergeron, HC  (2023-11-03)
Created
Shamovsky, V  (2023-06-20)
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