title: Insights into the mechanisms of membrane curvature and vesicle scission by the small GTPase Sar1 in the early secretory pathway.
abstract: The small GTPase protein Sar1 is known to be involved in both the initiation of COPII-coated vesicle formation and scission of the nascent vesicle from the endoplasmic reticulum. The molecular details for the mechanism of membrane remodeling by Sar1 remain unresolved. Here, we show that Sar1 transforms synthetic liposomes into structures of different morphologies including tubules and detached vesicles. We demonstrate that Sar1 alone is competent for vesicle scission in a manner that depends on the concentration of Sar1 molecules occupying the membrane. Sar1 molecules align on low-curvature membranes to form an extended lattice. The continuity of this lattice breaks down as the curvature locally increases. The smallest repeating unit constituting the ordered lattice is a Sar1 dimer. The three-dimensional structure of the Sar1 lattice was reconstructed by substituting spherical liposomes with galactoceramide lipid tubules of homogeneous diameter. These data suggest that Sar1 dimerization is responsible for the formation of constrictive membrane curvature. We propose a model whereby Sar1 dimers assemble into ordered arrays to promote membrane constriction and COPII-directed vesicle scission.
authors.affiliation: Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA. Electronic address: hhh09c@my.fsu.edu.
authors.forename: Hanaa
authors.initials: H
authors.lastname: Hariri
authors.affiliation: Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA. Electronic address: nb02c@fsu.edu.
authors.forename: Nilakshee
authors.initials: N
authors.lastname: Bhattacharya
authors.affiliation: Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306, USA. Electronic address: kmj09e@my.fsu.edu.
authors.forename: Kerri
authors.initials: K
authors.lastname: Johnson
authors.affiliation: Department of Physics, Florida State University, Tallahassee, FL 32306, USA. Electronic address: ajn10d@fsu.edu.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Noble
authors.affiliation: Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA; Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306, USA. Electronic address: sstagg@fsu.edu.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Stagg
mesh_terms: D022181:COP-Coated Vesicles / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D008081:Liposomes; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D055503:Protein Multimerization; D055571:Secretory Pathway / Q000502:physiology*
chemical_list: D008081:Liposomes; D006160:Guanosine Triphosphate; C513282:SAR1B protein, human; D020559:Monomeric GTP-Binding Proteins
keywords: ADE model; N-terminal helix; Sar1 lattice; dimerization; membrane scission