title: Structural basis for the geometry-driven localization of a small protein.
abstract: In bacteria, certain shape-sensing proteins localize to differently curved membranes. During sporulation in Bacillus subtilis, the only convex (positively curved) surface in the cell is the forespore, an approximately spherical internal organelle. Previously, we demonstrated that SpoVM localizes to the forespore by preferentially adsorbing onto slightly convex membranes. Here, we used NMR and molecular dynamics simulations of SpoVM and a localization mutant (SpoVM(P9A)) to reveal that SpoVM's atypical amphipathic α-helix inserts deeply into the membrane and interacts extensively with acyl chains to sense packing differences in differently curved membranes. Based on binding to spherical supported lipid bilayers and Monte Carlo simulations, we hypothesize that SpoVM's membrane insertion, along with potential cooperative interactions with other SpoVM molecules in the lipid bilayer, drives its preferential localization onto slightly convex membranes. Such a mechanism, which is distinct from that used by high curvature-sensing proteins, may be widely conserved for the localization of proteins onto the surface of cellular organelles.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Pennsylvania State University, Hershey, PA 17033;
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gill
authors.affiliation: Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Castaing
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA 94305;
authors.forename: Jen
authors.initials: J
authors.lastname: Hsin
authors.affiliation: Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; National Institutes of Health-Johns Hopkins University Graduate Partnerships Program, Baltimore, MD 21218; and.
authors.forename: Irene S
authors.initials: IS
authors.lastname: Tan
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Pennsylvania State University, Hershey, PA 17033;
authors.forename: Xingsheng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA 94305; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305 ramamurthiks@mail.nih.gov kchuang@stanford.edu ftian@psu.edu.
authors.forename: Kerwyn Casey
authors.initials: KC
authors.lastname: Huang
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Pennsylvania State University, Hershey, PA 17033; ramamurthiks@mail.nih.gov kchuang@stanford.edu ftian@psu.edu.
authors.forename: Fang
authors.initials: F
authors.lastname: Tian
authors.affiliation: Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; ramamurthiks@mail.nih.gov kchuang@stanford.edu ftian@psu.edu.
authors.forename: Kumaran S
authors.initials: KS
authors.lastname: Ramamurthi
mesh_terms: D001412:Bacillus subtilis / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008051:Lipid Bilayers / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008856:Microscopy, Fluorescence; D056004:Molecular Dynamics Simulation; D009010:Monte Carlo Method; D009154:Mutation; D011485:Protein Binding; D017433:Protein Structure, Secondary
chemical_list: D001426:Bacterial Proteins; D008051:Lipid Bilayers; C084307:spoVM protein, Bacillus subtilis; D049452:Green Fluorescent Proteins
keywords: ArfGAP1; DivIVA; SpoIVA; curvature sensing; lipid packing
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