title: N-terminal α-helix-independent membrane interactions facilitate adenovirus protein VI induction of membrane tubule formation.
abstract: Adenovirus disrupts endosomal membranes during cell entry. The membrane lytic capsid protein VI (pVI) facilitates entry by fragmenting membranes. Although an N-terminal amphipathic α-helix (VI-Φ) possesses similar membrane affinity as pVI, truncated protein lacking VI-Φ (VIΔ54) still possesses moderate membrane affinity. We demonstrate that incorporation of nickel-NTA lipids in membranes enhances the membrane affinity and the membrane lytic activity of VIΔ54. We also demonstrate that 3 predicted pVI α-helices within residues 54-114 associate with membranes, sitting roughly parallel to the membrane surface. His-tagged VIΔ54 is capable of fragmenting membranes similar to pVI and the VI-Φ peptide. Interestingly, neither VI-Φ nor His-tagged VIΔ54 can induce tubule formation in giant lipid vesicles as observed for pVI. These data suggest cooperativity between the amphipathic α-helix and residues in VIΔ54 to induce positive membrane curvature and tubule formation. These results provide additional details regarding the mechanism of nonenveloped virus membrane penetration.
authors.affiliation: Department of Microbiology and Immunology, Loyola University Chicago Stritch School of Medicine, Maywood, IL 60153, USA.
authors.forename: Oana
authors.initials: O
authors.lastname: Maier
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Wiethoff
mesh_terms: D000256:Adenoviridae / Q000502:physiology*; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion; D053586:Virus Internalization
chemical_list: D036022:Capsid Proteins; C090876:polypeptide VI, adenovirus