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Switch-like Responses of Two Cholesterol Sensors Do Not Require Protein Oligomerization in Membranes

Gay, Austin, Rye, Daphne, Radhakrishnan, Arun·2015·Biophysical Journal
DOI 10.1016/j.bpj.2015.02.008
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Abstract

Many cellular processes are sensitive to levels of cholesterol in specific membranes and show a strongly sigmoidal dependence on membrane composition. The sigmoidal responses of the cholesterol sensors involved in these processes could arise from several mechanisms, including positive cooperativity (protein effects) and limited cholesterol accessibility (membrane effects). Here, we describe a sigmoidal response that arises primarily from membrane effects due to sharp changes in the chemical activity of cholesterol. Our models for eukaryotic membrane-bound cholesterol sensors are soluble bacterial toxins that show an identical switch-like specificity for endoplasmic reticulum membrane cholesterol. We show that truncated versions of these toxins fail to form oligomers but still show sigmoidal binding to cholesterol-containing membranes. The nonlinear response emerges because interactions between bilayer lipids control cholesterol accessibility to toxins in a threshold-like fashion. Around these thresholds, the affinity of toxins for membrane cholesterol varies by >100-fold, generating highly cooperative lipid-dependent responses independently of protein-protein interactions. Such lipid-driven cooperativity may control the sensitivity of many cholesterol-dependent processes.

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  • Previous studies showed that in macrophages and hepatocytes Asters specifically recognize the accessible pool of plasma membrane cholesterol.

    “Previous studies showed that in macrophages (33) and hepatocytes (28) Asters specifically recognize the accessible pool of PM cholesterol (34, 35).”

    From Aster-dependent nonvesicular transport facilitates dietary cholesterol uptake (2023) · cites this paper as [35]

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Research works printed but not linked: 44

  1. Radhakrishnan, 2008, Switch-like control of SREBP-2 transport triggered by small changes in ER cholesterol: a delicate balance, Cell Metab., 8, 512, 10.1016/j.cmet.2008.10.008 · DOI · Paper page
  2. Sokolov, 2010, Accessibility of cholesterol in endoplasmic reticulum membranes and activation of SREBP-2 switch abruptly at a common cholesterol threshold, J. Biol. Chem., 285, 29480, 10.1074/jbc.M110.148254 · DOI · Paper page
  3. Das, 2013, Use of mutant 125I-perfringolysin O to probe transport and organization of cholesterol in membranes of animal cells, Proc. Natl. Acad. Sci. USA, 110, 10580, 10.1073/pnas.1309273110 · DOI · Paper page
  4. Brown, 1997, The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor, Cell, 89, 331, 10.1016/S0092-8674(00)80213-5 · DOI · Paper page
  5. Tweten, 2005, Cholesterol-dependent cytolysins, a family of versatile pore-forming toxins, Infect. Immun., 73, 6199, 10.1128/IAI.73.10.6199-6209.2005 · DOI
  6. Flanagan, 2009, Cholesterol exposure at the membrane surface is necessary and sufficient to trigger perfringolysin O binding, Biochemistry, 48, 3977, 10.1021/bi9002309 · DOI
  7. Nelson, 2008, How interaction of perfringolysin O with membranes is controlled by sterol structure, lipid structure, and physiological low pH: insights into the origin of perfringolysin O-lipid raft interaction, J. Biol. Chem., 283, 4632, 10.1074/jbc.M709483200 · DOI
  8. Radhakrishnan, 2004, Direct binding of cholesterol to the purified membrane region of SCAP: mechanism for a sterol-sensing domain, Mol. Cell, 15, 259, 10.1016/j.molcel.2004.06.019 · DOI · Paper page
  9. Radhakrishnan, 2007, Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: oxysterols block transport by binding to Insig, Proc. Natl. Acad. Sci. USA, 104, 6511, 10.1073/pnas.0700899104 · DOI · Paper page
  10. Heuck, 2010, The cholesterol-dependent cytolysin family of gram-positive bacterial toxins, Subcell. Biochem., 51, 551, 10.1007/978-90-481-8622-8_20 · DOI
  11. Rossjohn, 1997, Structure of a cholesterol-binding, thiol-activated cytolysin and a model of its membrane form, Cell, 89, 685, 10.1016/S0092-8674(00)80251-2 · DOI
  12. Polekhina, 2005, Insights into the action of the superfamily of cholesterol-dependent cytolysins from studies of intermedilysin, Proc. Natl. Acad. Sci. USA, 102, 600, 10.1073/pnas.0403229101 · DOI
  13. Bourdeau, 2009, Cellular functions and X-ray structure of anthrolysin O, a cholesterol-dependent cytolysin secreted by Bacillus anthracis, J. Biol. Chem., 284, 14645, 10.1074/jbc.M807631200 · DOI
  14. Xu, 2010, Crystal structure of cytotoxin protein suilysin from Streptococcus suis, Protein Cell, 1, 96, 10.1007/s13238-010-0012-3 · DOI
  15. Köster, 2013, Crystallization and X-ray crystallographic analysis of the cholesterol-dependent cytolysin listeriolysin O from Listeria monocytogenes, Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun., 69, 1212, 10.1107/S1744309113025761 · DOI
  16. Feil, 2014, Structural studies of Streptococcus pyogenes streptolysin O provide insights into the early steps of membrane penetration, J. Mol. Biol., 426, 785, 10.1016/j.jmb.2013.11.020 · DOI
  17. Farrand, 2010, Only two amino acids are essential for cytolytic toxin recognition of cholesterol at the membrane surface, Proc. Natl. Acad. Sci. USA, 107, 4341, 10.1073/pnas.0911581107 · DOI
  18. Ramachandran, 2005, The domains of a cholesterol-dependent cytolysin undergo a major FRET-detected rearrangement during pore formation, Proc. Natl. Acad. Sci. USA, 102, 7139, 10.1073/pnas.0500556102 · DOI
  19. Sato, 2013, Disulfide-bond scanning reveals assembly state and β-strand tilt angle of the PFO β-barrel, Nat. Chem. Biol., 9, 383, 10.1038/nchembio.1228 · DOI
  20. Tilley, 2005, Structural basis of pore formation by the bacterial toxin pneumolysin, Cell, 121, 247, 10.1016/j.cell.2005.02.033 · DOI
  21. Goldstein, 1983, Receptor-mediated endocytosis of low-density lipoprotein in cultured cells, Methods Enzymol., 98, 241, 10.1016/0076-6879(83)98152-1 · DOI
  22. Ishitsuka, 2011, Fluorescence image screening for chemical compounds modifying cholesterol metabolism and distribution, J. Lipid Res., 52, 2084, 10.1194/jlr.D018184 · DOI · Paper page
  23. Shimada, 2002, The C-terminal domain of perfringolysin O is an essential cholesterol-binding unit targeting to cholesterol-rich microdomains, Eur. J. Biochem., 269, 6195, 10.1046/j.1432-1033.2002.03338.x · DOI
  24. Cocklin, 2006, Real-time monitoring of the membrane-binding and insertion properties of the cholesterol-dependent cytolysin anthrolysin O from Bacillus anthracis, J. Mol. Recognit., 19, 354, 10.1002/jmr.784 · DOI
  25. Nakamura, 1995, Interaction of theta-toxin (perfringolysin O), a cholesterol-binding cytolysin, with liposomal membranes: change in the aromatic side chains upon binding and insertion, Biochemistry, 34, 6513, 10.1021/bi00019a032 · DOI
  26. Heuck, 2000, Mechanism of membrane insertion of a multimeric beta-barrel protein: perfringolysin O creates a pore using ordered and coupled conformational changes, Mol. Cell, 6, 1233, 10.1016/S1097-2765(00)00119-2 · DOI
  27. Keller, 2000, Saturated phospholipids with high melting temperatures form complexes with cholesterol in monolayers, J. Phys. Chem. B, 104, 7522, 10.1021/jp000958g · DOI
  28. Johnson, 2012, Modifications in perfringolysin O domain 4 alter the cholesterol concentration threshold required for binding, Biochemistry, 51, 3373, 10.1021/bi3003132 · DOI
  29. Radhakrishnan, 2005, Condensed complexes in vesicles containing cholesterol and phospholipids, Proc. Natl. Acad. Sci. USA, 102, 12662, 10.1073/pnas.0506043102 · DOI
  30. Radhakrishnan, 2000, Chemical activity of cholesterol in membranes, Biochemistry, 39, 8119, 10.1021/bi0005097 · DOI · Paper page
  31. Lange, 2013, Stability and stoichiometry of bilayer phospholipid-cholesterol complexes: relationship to cellular sterol distribution and homeostasis, Biochemistry, 52, 6950, 10.1021/bi400862q · DOI · Paper page
  32. McConnell, 2006, Theory of the deuterium NMR of sterol-phospholipid membranes, Proc. Natl. Acad. Sci. USA, 103, 1184, 10.1073/pnas.0510514103 · DOI
  33. Ratajczak, 2009, Ordered nanoclusters in lipid-cholesterol membranes, Phys. Rev. Lett., 103, 028103, 10.1103/PhysRevLett.103.028103 · DOI
  34. Zheng, 2005, Ultrafast dynamics of solute-solvent complexation observed at thermal equilibrium in real time, Science, 309, 1338, 10.1126/science.1116213 · DOI
  35. Okonogi, 2002, Two fatty acids can replace one phospholipid in condensed complexes with cholesterol, Biochim. Biophys. Acta, 1564, 1, 10.1016/S0005-2736(02)00451-0 · DOI
  36. Ali, 2007, Assess the nature of cholesterol-lipid interactions through the chemical potential of cholesterol in phosphatidylcholine bilayers, Proc. Natl. Acad. Sci. USA, 104, 5372, 10.1073/pnas.0611450104 · DOI
  37. Olsen, 2013, The structural basis of cholesterol accessibility in membranes, Biophys. J., 105, 1838, 10.1016/j.bpj.2013.08.042 · DOI
  38. Veatch, 2006, Closed-loop miscibility gap and quantitative tie-lines in ternary membranes containing diphytanoyl PC, Biophys. J., 90, 4428, 10.1529/biophysj.105.080283 · DOI
  39. Veatch, 2004, Liquid domains in vesicles investigated by NMR and fluorescence microscopy, Biophys. J., 86, 2910, 10.1016/S0006-3495(04)74342-8 · DOI
  40. Im, 2005, Structural mechanism for sterol sensing and transport by OSBP-related proteins, Nature, 437, 154, 10.1038/nature03923 · DOI
  41. Kwon, 2009, Structure of N-terminal domain of NPC1 reveals distinct subdomains for binding and transfer of cholesterol, Cell, 137, 1213, 10.1016/j.cell.2009.03.049 · DOI · Paper page
  42. Ohvo, 1996, Cyclodextrin-mediated removal of sterols from monolayers: effects of sterol structure and phospholipids on desorption rate, Biochemistry, 35, 8018, 10.1021/bi9528816 · DOI
  43. Motamed, 2011, Identification of luminal Loop 1 of Scap protein as the sterol sensor that maintains cholesterol homeostasis, J. Biol. Chem., 286, 18002, 10.1074/jbc.M111.238311 · DOI
  44. Lange, 2008, Cholesterol homeostasis and the escape tendency (activity) of plasma membrane cholesterol, Prog. Lipid Res., 47, 319, 10.1016/j.plipres.2008.03.001 · DOI

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Metadata

Authors
Gay, A., Rye, D., & Radhakrishnan, A.
Venue
Biophysical Journal
Publisher
Elsevier BV
Published
2015-03
Volume
108
Issue
6
Pages
1459-1469
ISSN
0006-3495
DOI
10.1016/j.bpj.2015.02.008
Cited by
86
References
0
Language
en
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