Varkey, JobinZhang, JiantaoKim, JunghyunGeorge, GincyHe, GuijuanBelov, George A.Langen, RalfWang, Xiaofeng2021-01-042021-01-042020-12-18Varkey, J.; Zhang, J.; Kim, J.; George, G.; He, G.; Belov, G.; Langen, R.; Wang, X. An Amphipathic Alpha-Helix Domain from Poliovirus 2C Protein Tubulate Lipid Vesicles. Viruses 2020, 12, 1466.http://hdl.handle.net/10919/101724Positive-strand RNA viruses universally remodel host intracellular membranes to form membrane-bound viral replication complexes, where viral offspring RNAs are synthesized. In the majority of cases, viral replication proteins are targeted to and play critical roles in the modulation of the designated organelle membranes. Many viral replication proteins do not have transmembrane domains, but contain single or multiple amphipathic alpha-helices. It has been conventionally recognized that these helices serve as an anchor for viral replication protein to be associated with membranes. We report here that a peptide representing the amphipathic α-helix at the N-terminus of the poliovirus 2C protein not only binds to liposomes, but also remodels spherical liposomes into tubules. The membrane remodeling ability of this amphipathic alpha-helix is similar to that recognized in other amphipathic alpha-helices from cellular proteins involved in membrane remodeling, such as BAR domain proteins. Mutations affecting the hydrophobic face of the amphipathic alpha-helix severely compromised membrane remodeling of vesicles with physiologically relevant phospholipid composition. These mutations also affected the ability of poliovirus to form plaques indicative of reduced viral replication, further underscoring the importance of membrane remodeling by the amphipathic alpha-helix in possible relation to the formation of viral replication complexes.application/pdfenCreative Commons Attribution 4.0 Internationalpoliovirus 2C proteinpositive-strand RNA virusmembrane remodelingamphipathic alpha-helixviral replication complexAn Amphipathic Alpha-Helix Domain from Poliovirus 2C Protein Tubulate Lipid VesiclesArticle - Refereed2020-12-24Viruseshttps://doi.org/10.3390/v12121466