Editorial Cite This: Chem. Rev. 2019, 119, 5535−5536
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Introduction: Biomembrane Structure, Dynamics, and Reactions
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for examining the passive transport of small hydrophobic and hydrophilic substances across membranes. The permeability of membranes to small molecules such as water and oxygen is further addressed by Venable and colleagues from a computer simulations perspective; the comparison of simulations and experiments highlights challenges for force-field development and the usefulness of computations for interpreting experimental data. Ion channels are the subject of the review by Oakes and Domene, who focus on the interaction between anesthetics, ion channels, and membranes, and on the usefulness of computational biophysics approaches for understanding how anesthetic agents work. Hall and colleagues discuss water permeability and regulation by Aquaporin 0, AQP0, from the history of aquaporin studies to recent developments in experimental and molecular dynamics studies, including the connection between experiments and simulations and lipid interactions of AQP0. The frontier that membranes present to the outside world can be compromised by membrane-permeabilizing peptides, of which melittin, a small peptide derived from bee venom, is a classical example. Guha and colleagues review the diversity of membrane-permeabilizing peptides and the experimental and theoretical approaches for studying them, and the complexity of the mechanistic landscape of membrane-permeabilizing peptides. Interactions between proteins and lipids from the surrounding membrane can shape the reaction coordinate of membrane-embedded enzymes. An intriguing example of tight coupling between the lipid membrane and the membrane protein is that of intramembrane proteases, enzymes that are bound to the membrane where they cleave transmembrane helical substrates. In the case of GlpG, the rhomboid intramembrane protease from Escherichia coli, lipids appear to impact the reaction coordinate of substrate cleavage by rhomboids in a protein-specific manner, as rhomboids from different bacteria respond differently to specific compositions of the lipid membrane.9,10 Another prominent example is that of the mechanosensitive potassium ion channel TRAAK, whose opening and closing might involve changes in lateral access by a lipid alkyl chain.11 Computer simulations are a valuable approach for understanding how interactions with lipids impact membrane protein function. The review by Muller and colleagues documents computer simulation approaches for studying lipid membranes and membrane proteins embedded in lipid bilayersincluding the membrane mimetic model derived in their laboratory, lipid−protein interactions in membraneembedded proteins and peripheral membrane proteins, and the complex coupling between lipids and membrane proteins. Bondar and Lemieux discuss reactions at membrane interfaces, particularly how lipids and hydrogen bonding may influence reaction coordinates of membrane-embedded proteins.
ell membranes have complex structure and dynamics and host reactions essential for the biological cell. There is a remarkable diversity in the lipid composition of cell membranes, with organelles, membrane domains, and membrane leaflets being distinguished by the subsets of lipids they include1 and with bacterial species having distinct lipid compositions of their membranes.2 Membrane proteins bound to lipid membranes perform essential cellular functions, such as transport of ions and larger solutes, cell signaling, and catalyzing chemical reactions. This thematic issue of Chemical Reviews highlights the current status, perspectives, and challenges in theoretical and experimental studies of lipid membranes and membrane proteins. Lipid membranes largely shape the structure of membrane proteins.3 How membrane proteins are assembled within the heterogeneous environment of the membranes, how misfolding is recognized and dealt with in the cell, and how misfolded proteins can be stabilized with special compounds, are fascinating questions addressed by Marinko and colleagues. Enkavi and colleagues build upon a historical overview of cell membrane models and computer simulations and give a comprehensive review of lipid membranes and membrane proteins that are particularly important to understand, properties of biomembranes and reactions in biomembranes, and multiscale simulations of biomembranes. Membrane-embedded receptor proteins mediate communication across the cell membrane. Prominent examples here are the G Protein Coupled Receptors (GPCRs), seven-helical membrane proteins which mediate the response of the cell to a variety of external stimuli, including light, hormones, and opiates.4,5 GPCRs are dynamic proteins, and early experiments on the visual rhodopsin GPCR indicated that the conformational transition from an inactive to an active state, in which the receptor can bind the G protein, is influenced by the lipid composition of the surrounding lipid membrane.6 Lipid− protein interactions of GPCRs and of a large set of other membrane proteins−including membrane transporters and receptors, viral proteins, and the C99 substrate of γ-secretase are addressed by Corradi and colleagues. Cheng and Smith discuss membrane signaling and mechanisms for membrane signaling in a broad perspective of how signal transduction is shaped by physical and mechanical properties of the lipid membrane and by the organization of the membrane. Paul and Hristova focus on receptor tyrosine kinases (RTK), single-pass membrane receptors involved that can interact with each otherthe complex RTK interactome they introduce, a concept thought essential for understanding the biology of these receptors. Transport of ions and other small molecules across the membrane is involved in essential cellular processes such as cell signaling and maintenance of electrochemical gradients across membranes, and membrane transporter proteins are of major interest for drug development,7 including for the treatment of neuropathic pain with sodium ion channel blockers. 8 Hannesschlaeger and colleagues present a multislab model © 2019 American Chemical Society
Special Issue: Biomembrane Structure, Dynamics, and Reactions Published: May 8, 2019 5535
DOI: 10.1021/acs.chemrev.9b00093 Chem. Rev. 2019, 119, 5535−5536
Chemical Reviews
Editorial
(4) Rosenbaum, D. M.; Rasmussen, S. G. F.; Kobilka, B. K. The structure and function of G-protein-coupled receptors. Nature 2009, 459, 356. (5) Al-Hasani, R.; Bruchas, M. R. Molecular mechanisms of opioid receptor-dependent signaling and behavior. Anesthesiology 2011, 115, 1363. (6) Brown, M. F. Modulation of rhodopsin function by properties of the membrane bilayer. Chem. Phys. Lipids 1994, 73, 159. (7) Giacomini, K. M.; Huang, S.-M.; Tweedie, D. J.; Benet, L. Z.; Brower, K. L. R.; Chu, X.; Dahlin, A.; Evers, R.; Fischer, V.; et al. Membrane transporters in drug development. Nat. Rev. Drug Discovery 2010, 9, 215. (8) Priest, B. T.; Kaczorowski, G. J. Blocking sodium channels to treat neuropathic pain. Expert Opin. Ther. Targets 2007, 11, 291. (9) Urban, S.; Wolfe, M. S. Reconstitution of intramembrane proteolysis in vitro reveals that pure rhomboid is sufficient for catalysis and specificity. Proc. Natl. Acad. Sci. U. S. A. 2005, 102, 1883. (10) Bondar, A.-N. Biophysical mechanism of rhomboid proteolysis: setting a foundation for therapeutics. Semin. Cell Dev. Biol. 2016, 60, 46. (11) Brohawn, S. G.; Campbell, E. B.; MacKinnon, R. Physical mechanism for gating and mechanosensitivity of the human TRAAK K+ channel. Nature 2014, 516, 126.
Developments in computational approaches and computer power enable computer simulations of complex lipid mixtures and simulations with multiple proteins, bringing computational models closer to realistic biomembranes. Marrink and colleagues review the currents status and challenges of force fields for describing lipid membrane systems, the applicability of computer simulation approaches for studying systems of increasing complexity, and prominent examples that range from relatively simple membrane protein−lipid bilayer systems to plasma membrane models to systems as complex as, e.g., viral envelopes. The key issue of developing force fields for accurate descriptions of lipid membrane systems is further discussed by Leonard and colleagues, who review lipid force fields with their strengths and limitations in predicting various bilayer properties, including for complex membrane systems. I anticipate that the wealth of information from the comprehensive reviews of this thematic issue of Chemical Reviews will serve as a valuable reference for the field of biomembranes.
Ana-Nicoleta Bondar* Freie Universität Berlin, Department of Physics, Theoretical Molecular Biophysics Group, Berlin, Germany
AUTHOR INFORMATION Corresponding Author
*E-mail:
[email protected]. ORCID
Ana-Nicoleta Bondar: 0000-0003-2636-9773 Notes
Views expressed in this editorial are those of the author and not necessarily the views of the ACS. Biography Guest Editor Ana-Nicoleta Bondar (A-NB) leads the Theoretical Molecular Biophysics Group at the Department of Physics of the Freie Universität Berlin. She completed her doctoral research at the University of Heidelberg and the German Cancer Research Center Research Center (DKFZ) Heidelberg and obtained her doctoral degree from the University of Heidelberg in 2004. After postdoctoral research at the University of Heidelberg and the University of California, Irvine, in 2010, A-NB joined the Freie Universität Berlin. A-NB’s research interests include membrane protein function, hydrogen bonding, and computer simulations of membranes and membrane proteins.
ACKNOWLEDGMENTS A-NB is supported in part by the Freie Universität Berlin within the Excellence Initiative of the German Research Foundation. I thank Joachim Heberle for the invitation to guest-edit the special issue, and all authors whose contributions made the thematic issue possible. REFERENCES (1) van Meer, G.; Voelker, D. R.; Feigenson, G. W. Membrane lipids: where they are and how they behave. Nat. Rev. Mol. Cell Biol. 2008, 9, 112. (2) Sohlenkamp, C.; Geiger, O. Bacterial membrane lipids: diversity in structure and pathways. FEMS Microbiol. Rev. 2016, 40, 133. (3) White, S. H.; Ladokhin, A. S.; Jayasinghe, S.; Hristova, K. How membranes shape protein structure. J. Biol. Chem. 2001, 276, 32395. 5536
DOI: 10.1021/acs.chemrev.9b00093 Chem. Rev. 2019, 119, 5535−5536
