2024-03-29T07:09:05Zhttps://repositori.uji.es/oai/requestoai:repositori.uji.es:10234/1589782024-03-26T08:28:50Zcom_10234_2507com_10234_9col_10234_6973
00925njm 22002777a 4500
dc
Largo, Eneko
author
Verdiá Báguena, Carmen
author
Aguilella, Vicente
author
Nieva, José L.
author
Alcaraz, Antonio
author
2016-01
Viroporins comprise a family of non-structural proteins that play significant and diverse roles during the replication cycle of many animal viruses. Consequently, they have become promising targets for inhibitory drug and vaccine development. Structure–function traits common to all members of the family are their small size (ca. 60–120 aa), high hydrophobicity, and the presence of helical domains that transverse the membrane and assemble into oligomeric-permeating structures therein. The possibility that viroporins show in particular conditions any kind of specificity in the transport of ions and small solutes remains a point of contention in the field. Here we have approached this issue using the Classical Swine Fever Virus (CSFV) protein p7 viroporin as a model. We have previously reported that CSFV-p7 induces release of ANTS (MW: 427.33) from lipid vesicles that emulate the Endoplasmic Reticulum (ER) membrane, and that this process is dependent on pH, modulated by the lipid composition, and recreated by a C-terminal transmembrane helix. Here we have assayed CSFV-p7 for its capacity to form ion-conducting channels in ER-like planar lipid membranes, and established whether this activity is subject to regulation by the same factors. The analysis of electrophysiological recordings in ER membrane surrogates suggests that CSFV-p7 forms pores wide enough to allow ANTS release. Moreover, we were able to discriminate between two pore structures with slightly different sizes and opposite ion selectivities. The fact that the relative abundances of each pore type depend crucially on membrane composition strengthens the view that the physicochemical properties of the lipid bilayers present in the cell endomembrane system modulate viroporin activity.
LARGO, Eneko, et al. Ion channel activity of the CSFV p7 viroporin in surrogates of the ER lipid bilayer. Biochimica et Biophysica Acta (BBA)-Biomembranes, 2016, vol. 1858, no 1, p. 30-37
0005-2736
http://hdl.handle.net/10234/158978
http://dx.doi.org/10.1016/j.bbamem.2015.10.007
Viroporins
Ion channels
Planar membranes
Lipid vesicles
Ion channel activity of the CSFV p7 viroporin in surrogates of the ER lipid bilayer