title: ERp29 triggers a conformational change in polyomavirus to stimulate membrane binding.
abstract: Membrane penetration of nonenveloped viruses is a poorly understood process. We have investigated early stages of this process by studying the conformational change experienced by polyomavirus (Py) in the lumen of the endoplasmic reticulum (ER), a step that precedes its transport into the cytosol. We show that a PDI-like protein, ERp29, exposes the C-terminal arm of Py's VP1 protein, leading to formation of a hydrophobic particle that binds to a lipid bilayer; this reaction likely mimics initiation of Py penetration across the ER membrane. Expression of a dominant-negative ERp29 decreases Py infection, indicating ERp29 facilitates viral infection. Interestingly, cholera toxin, another toxic agent that crosses the ER membrane into the cytosol, is unfolded by PDI in the ER. Our data thus identify an ER factor that mediates membrane penetration of a nonenveloped virus and suggest that PDI family members are generally involved in ER remodeling reactions.
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, 4643 Medical Sciences II, 1335 East Catherine Street, Ann Arbor, Michigan 48109, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Magnuson
authors.forename: Emily K
authors.initials: EK
authors.lastname: Rainey
authors.forename: Thomas
authors.initials: T
authors.lastname: Benjamin
authors.forename: Mikhail
authors.initials: M
authors.lastname: Baryshev
authors.forename: Souren
authors.initials: S
authors.lastname: Mkrtchian
authors.forename: Billy
authors.initials: B
authors.lastname: Tsai
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000378:metabolism*; D002460:Cell Line; D002772:Cholera Toxin / Q000737:chemistry / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism / Q000821:virology; D004285:Dogs; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000821:virology; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D008051:Lipid Bilayers / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism; D051379:Mice; D011120:Polyomavirus / Q000378:metabolism*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D051381:Rats
chemical_list: D036022:Capsid Proteins; C110909:Erp29 protein, rat; D006360:Heat-Shock Proteins; D008051:Lipid Bilayers; D008081:Liposomes; C062481:VP1 protein, polyomavirus; D002772:Cholera Toxin