title: Pro-apoptotic Bax molecules densely populate the edges of membrane pores.
abstract: How the pro-apoptotic Bax protein permeabilizes the mitochondrial outer membrane is not fully understood. Previously, using cryo-electron microscopy (cryo-EM), we showed that activated Bax forms large, growing pores. Whether formed in liposomes or in mitochondrial outer membranes, Bax-induced pores exhibit the same morphology, with negative curvature flanking the edges and with no visible protein structure protruding from the membranes. Here we used cryo-EM to show that gold-labeled Bax molecules, after activation by Bid, became localized strictly at pore edges. This argues that Bax acts at short range to deform the membrane. Also, Bax molecules populated the walls of both small and large pores at the same density, implying that Bax is continuously recruited to the pores as they widen. Moreover, because all Bax molecules became oligomerized after membrane insertion, we infer that Bax oligomers are present at pore edges. We suggest that oligomerization may promote pore enlargement.
authors.affiliation: La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kuwana
authors.affiliation: University of California San Diego Cryo-EM Core Facility, La Jolla, CA 92037, USA.
authors.forename: Norman H
authors.initials: NH
authors.lastname: Olson
authors.affiliation: La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
authors.forename: William B
authors.initials: WB
authors.lastname: Kiosses
authors.affiliation: La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
authors.forename: Bjoern
authors.initials: B
authors.lastname: Peters
authors.affiliation: La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
authors.forename: Donald D
authors.initials: DD
authors.lastname: Newmeyer
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D020285:Cryoelectron Microscopy; D051336:Mitochondrial Membranes / Q000737:chemistry* / Q000502:physiology*; D010539:Permeability; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D051028:bcl-2-Associated X Protein