Membrane Protein Assembly into Nanodiscs

Overview

Journal FEBS Lett

Specialty Biochemistry

Date 2009 Oct 20

PMID 19836392

Citations 337

Authors

Timothy H Bayburt

Stephen G Sligar

Affiliations

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Abstract

Nanodiscs are soluble nanoscale phospholipid bilayers which can self-assemble integral membrane proteins for biophysical, enzymatic or structural investigations. This means for rendering membrane proteins soluble at the single molecule level offers advantages over liposomes or detergent micelles in terms of size, stability, ability to add genetically modifiable features to the Nanodisc structure and ready access to both sides of the phospholipid bilayer domain. Thus the Nanodisc system provides a novel platform for understanding membrane protein function. We provide an overview of the Nanodisc approach and document through several examples many of the applications to the study of the structure and function of integral membrane proteins.

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References

Heyn M, Cherry R, Dencher N . Lipid--protein interactions in bacteriorhodopsin--dimyristoylphosphatidylcholine vesicles. Biochemistry. 1981; 20(4):840-9. DOI: 10.1021/bi00507a029. View

Civjan N, Bayburt T, Schuler M, Sligar S . Direct solubilization of heterologously expressed membrane proteins by incorporation into nanoscale lipid bilayers. Biotechniques. 2003; 35(3):556-60, 562-3. DOI: 10.2144/03353rr02. View

Lyukmanova E, Shenkarev Z, Paramonov A, Sobol A, Ovchinnikova T, Chupin V . Lipid-protein nanoscale bilayers: a versatile medium for NMR investigations of membrane proteins and membrane-active peptides. J Am Chem Soc. 2008; 130(7):2140-1. DOI: 10.1021/ja0777988. View

Catte A, Patterson J, Jones M, Jerome W, Bashtovyy D, Su Z . Novel changes in discoidal high density lipoprotein morphology: a molecular dynamics study. Biophys J. 2006; 90(12):4345-60. PMC: 1471865. DOI: 10.1529/biophysj.105.071456. View

Katzen F, Fletcher J, Yang J, Kang D, Peterson T, Cappuccio J . Insertion of membrane proteins into discoidal membranes using a cell-free protein expression approach. J Proteome Res. 2008; 7(8):3535-42. DOI: 10.1021/pr800265f. View

Fotiadis D, Liang Y, Filipek S, Saperstein D, Engel A, Palczewski K . The G protein-coupled receptor rhodopsin in the native membrane. FEBS Lett. 2004; 564(3):281-288. PMC: 1393389. DOI: 10.1016/S0014-5793(04)00194-2. View

Denisov I, Grinkova Y, Lazarides A, Sligar S . Directed self-assembly of monodisperse phospholipid bilayer Nanodiscs with controlled size. J Am Chem Soc. 2004; 126(11):3477-87. DOI: 10.1021/ja0393574. View

Denisov I, Baas B, Grinkova Y, Sligar S . Cooperativity in cytochrome P450 3A4: linkages in substrate binding, spin state, uncoupling, and product formation. J Biol Chem. 2007; 282(10):7066-76. DOI: 10.1074/jbc.M609589200. View

Bayburt T, Sligar S . Self-assembly of single integral membrane proteins into soluble nanoscale phospholipid bilayers. Protein Sci. 2003; 12(11):2476-81. PMC: 2366955. DOI: 10.1110/ps.03267503. View

10.

Dalal K, Nguyen N, Alami M, Tan J, Moraes T, Lee W . Structure, binding, and activity of Syd, a SecY-interacting protein. J Biol Chem. 2009; 284(12):7897-902. PMC: 2658082. DOI: 10.1074/jbc.M808305200. View

11.

Nath A, Koo P, Rhoades E, Atkins W . Allosteric effects on substrate dissociation from cytochrome P450 3A4 in nanodiscs observed by ensemble and single-molecule fluorescence spectroscopy. J Am Chem Soc. 2008; 130(47):15746-7. PMC: 2649694. DOI: 10.1021/ja805772r. View

12.

Denisov I, Grinkova Y, Baas B, Sligar S . The ferrous-dioxygen intermediate in human cytochrome P450 3A4. Substrate dependence of formation and decay kinetics. J Biol Chem. 2006; 281(33):23313-8. DOI: 10.1074/jbc.M605511200. View

13.

Das A, Zhao J, Schatz G, Sligar S, Van Duyne R . Screening of type I and II drug binding to human cytochrome P450-3A4 in nanodiscs by localized surface plasmon resonance spectroscopy. Anal Chem. 2009; 81(10):3754-9. PMC: 4757437. DOI: 10.1021/ac802612z. View

14.

Blanchette C, Cappuccio J, Kuhn E, Segelke B, Benner W, Chromy B . Atomic force microscopy differentiates discrete size distributions between membrane protein containing and empty nanolipoprotein particles. Biochim Biophys Acta. 2008; 1788(3):724-31. DOI: 10.1016/j.bbamem.2008.11.019. View

15.

Bayburt T, Sligar S . Single-molecule height measurements on microsomal cytochrome P450 in nanometer-scale phospholipid bilayer disks. Proc Natl Acad Sci U S A. 2002; 99(10):6725-30. PMC: 124470. DOI: 10.1073/pnas.062565599. View

16.

Carlson J, Jonas A, Sligar S . Imaging and manipulation of high-density lipoproteins. Biophys J. 1997; 73(3):1184-9. PMC: 1181017. DOI: 10.1016/S0006-3495(97)78150-5. View

17.

Shaw A, McLean M, Sligar S . Phospholipid phase transitions in homogeneous nanometer scale bilayer discs. FEBS Lett. 2004; 556(1-3):260-4. DOI: 10.1016/s0014-5793(03)01400-5. View

18.

Li Y, Kijac A, Sligar S, Rienstra C . Structural analysis of nanoscale self-assembled discoidal lipid bilayers by solid-state NMR spectroscopy. Biophys J. 2006; 91(10):3819-28. PMC: 1630456. DOI: 10.1529/biophysj.106.087072. View

19.

Whorton M, Jastrzebska B, Park P, Fotiadis D, Engel A, Palczewski K . Efficient coupling of transducin to monomeric rhodopsin in a phospholipid bilayer. J Biol Chem. 2007; 283(7):4387-94. PMC: 2651572. DOI: 10.1074/jbc.M703346200. View

20.

Shih A, Arkhipov A, Freddolino P, Freddolino L, Sligar S, Schulten K . Assembly of lipids and proteins into lipoprotein particles. J Phys Chem B. 2007; 111(38):11095-104. DOI: 10.1021/jp072320b. View