Reactome | SH pentamer transports K+

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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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 Araujo, GC, Silva, RH, Scott, LP, Araujo, AS, Souza, FP, de Oliveira, RJ	J Mol Model	2016
25100835	Inhibition of the human respiratory syncytial virus small hydrophobic protein and structural variations in a bicelle environment Li, Y, To, J, Verdiá-Báguena, C, Dossena, S, Surya, W, Huang, M, Paulmichl, M, Liu, DX, Aguilella, VM, Torres, J	J Virol	2014
23229815	Human respiratory syncytial virus viroporin SH: a viral recognition pathway used by the host to signal inflammasome activation Triantafilou, K, Kar, S, Vakakis, E, Kotecha, S, Triantafilou, M	Thorax	2013
20471980	Direct visualization of the small hydrophobic protein of human respiratory syncytial virus reveals the structural basis for membrane permeability Carter, SD, Dent, KC, Atkins, E, Foster, TL, Verow, M, Gorny, P, Harris, M, Hiscox, JA, Ranson, NA, Griffin, S, Barr, JN	FEBS Lett	2010
22621926	The small hydrophobic protein of the human respiratory syncytial virus forms pentameric ion channels Gan, SW, Tan, E, Lin, X, Yu, D, Wang, J, Tan, GM, Vararattanavech, A, Yeo, CY, Soon, CH, Soong, TW, Pervushin, K, Torres, J	J Biol Chem	2012
18369195	Structure and ion channel activity of the human respiratory syncytial virus (hRSV) small hydrophobic protein transmembrane domain Gan, SW, Ng, L, Lin, X, Gong, X, Torres, J	Protein Sci	2008