278
Views
4
CrossRef citations to date
0
Altmetric
Research Articles

Predicting interfacial hot-spot residues that stabilize protein-protein interfaces in oligomeric membrane-toxin pores through hydrogen bonds and salt bridges

ORCID Icon, &
Pages 20-34 | Received 04 Aug 2019, Accepted 28 Nov 2019, Published online: 29 Jan 2020

References

  • Adhikari, R. P., Thompson, C. D., Aman, M. J., & Lee, J. C. (2016). Protective efficacy of a novel alpha hemolysin subunit vaccine (AT62) against Staphylococcus aureus skin and soft tissue infections. Vaccine, 34(50), 6402–6407. doi:10.1016/j.vaccine.2016.09.061
  • Agrawal, A., Apoorva, K., & Ayappa, K. G. (2017). Transmembrane oligomeric intermediates of pore forming toxin cytolysin a determine leakage kinetics. RSC Advances, 7(82), 51750–51762. doi:10.1039/C7RA07304F
  • Alford, R. F., Leaver-Fay, A., Jeliazkov, J. R., O’Meara, M. J., DiMaio, F. P., Park, H., … Gray, J. J. (2017). The Rosetta all-atom energy function for macromolecular modeling and design. Journal of Chemical Theory and Computation, 13(6), 3031–3048. doi:10.1021/acs.jctc.7b00125
  • Allen, M. P., & Tildesley, D. J. (2017). Computer simulation of liquids (2nd ed.). Oxford: Oxford University Press.
  • Badarau, A., Rouha, H., Malafa, S., Logan, D. T., Håkansson, M., Stulik, L., … Nagy, E. (2015). Structure-function analysis of heterodimer formation, oligomerization, and receptor binding of the Staphylococcus aureus bi-component toxin LukGH. Journal of Biological Chemistry, 290(1), 142–156. doi:10.1074/jbc.M114.598110
  • Baker, N. A., Sept, D., Joseph, S., Holst, M. J., & McCammon, J. A. (2001). Electrostatics of nanosystems: Application to microtubules and the ribosome. Proceedings of the National Academy of Sciences, 98(18), 10037–10041. doi:10.1073/pnas.181342398
  • Barlow, D. J., & Thornton, J. M. (1983). Ion-pairs in proteins. Journal of Molecular Biology, 168(4), 867–885. doi:10.1016/s0022-2836(83)80079-5
  • Basu, S., & Mukharjee, D. (2017). Salt-bridge networks within globular and disordered proteins: Characterizing trends for designable interactions. Journal of Molecular Modeling, 23(7), 206. doi:10.1007/s00894-017-3376-y
  • Blair, J. M., Webber, M. A., Baylay, A. J., Ogbolu, D. O., & Piddock, L. J. (2015). Molecular mechanisms of antibiotic resistance. Nature Reviews Microbiology, 13(1), 42–51. doi:10.1038/nrmicro3380
  • Böckmann, R. A., & Caflisch, A. (2005). Spontaneous formation of detergent micelles around the outer membrane protein OmpX. Biophysical Journal., 88(5), 3191–3204. doi:10.1529/biophysj.105.060426
  • Bosshard, H. R., Marti, D. N., & Jelesarov, I. (2004). Protein stabilization by salt bridges: Concepts, experimental approaches and clarification of some misunderstandings. Journal of Molecular Recognition, 17(1), 1–16. doi:10.1002/jmr.657
  • Bussi, G., Donadio, D., & Parrinello, M. (2007). Canonical sampling through velocity rescaling. Journal of Chemical Physics., 126(1), 014101. doi:10.1063/1.2408420
  • Chen, W., OuYang, B., & Chou, J. J. (2019). Critical effect of the detergent: Protein ratio on the formation of the hepatitis C virus p7 channel. Biochemistry, 58(37), 3834–3837. doi:10.1021/acs.biochem.9b00636
  • Clarke, J., Wu, H. C., Jayasinghe, L., Patel, A., Reid, S., & Bayley, H. (2009). Continuous base identification for single-molecule nanopore DNA sequencing. Nature Nanotechnology, 4(4), 265–270. doi:10.1038/nnano.2009.12
  • Crooks, G. E., Hon, G., Chandonia, J. M., & Brenner, S. E. (2004). WebLogo: A sequence logo generator. Genome Research, 14(6), 1188–1190. doi:10.1101/gr.849004
  • Czuczman, M. A., Fattouh, R., van Rijn, J. M., Canadien, V., Osborne, S., Muise, A. M., … Brumell, J. H. (2014). Listeria monocytogenes exploits efferocytosis to promote cell-to-cell spread. Nature, 509(7499), 230–234. doi:10.1038/nature13168
  • Darden, T., York, D., & Pedersen, L. (1993). Particle mesh Ewald: An nlog(n) method for Ewald sums in large systems. The Journal of Chemical Physics, 98(12), 10089–10092. doi:10.1063/1.464397
  • Debiec, K. T., Gronenborn, A. M., & Chong, L. T. (2014). Evaluating the strength of salt bridges: A comparison of current biomolecular force fields. The Journal of Physical Chemistry B, 118(24), 6561–6569. doi:10.1021/jp500958r
  • Desikan, R., Maiti, P. K., & Ayappa, K. G. (2017). Assessing the structure and stability of transmembrane oligomeric intermediates of an α-helical toxin. Langmuir, 33(42), 11496–11510. doi:10.1021/acs.langmuir.7b02277
  • Desikan, R., Patra, S. M., Sarthak, K., Maiti, P. K., & Ayappa, K. G. (2017). Comparison of coarse-grained (martini) and atomistic molecular dynamics simulations of α and β toxin nanopores in lipid membranes. Journal of Chemical Sciences, 129(7), 1017–1030. doi:10.1007/s12039-017-1316-0
  • Desiraju, G., & Steiner, T. (2001). The weak hydrogen bond: In structural chemistry and biology. Oxford: Oxford University Press. Retrieved from 10.1093/acprof:oso/9780198509707.001.0001
  • Donald, J. E., Kulp, D. W., & DeGrado, W. F. (2011). Salt bridges: Geometrically specific, designable interactions. Proteins: Structure, Function, and Bioinformatics, 79(3), 898–915. doi:10.1002/prot.22927
  • Drücker, P., Iacovache, I., Bachler, S., Zuber, B., Babiychuk, E. B., Dittrich, P. S., & Draeger, A. (2019). Membrane deformation and layer-by-layer peeling of giant vesicles induced by the pore forming toxin pneumolysin. Biomaterials Science, 7(9), 3693–3705. doi:10.1039/C9BM00134D
  • Eisenhaber, F., Lijnzaad, P., Argos, P., Sander, C., & Scharf, M. (1995). The double cubic lattice method: Efficient approaches to numerical integration of surface area and volume and to dot surface contouring of molecular assemblies. Journal of Computational Chemistry, 16(3), 273–284. doi:10.1002/jcc.540160303
  • Erijman, A., Rosenthal, E., & Shifman, J. M. (2014). How structure defines affinity in protein-protein interactions. PLoS One, 9(10), e110085. doi:10.1371/journal.pone.0110085
  • Escajadillo, T., & Nizet, V. (2018). Pharmacological targeting of pore-forming toxins as adjunctive therapy for invasive bacterial infection. Toxins, 10(12), 542. doi:10.3390/toxins10120542
  • Fang, R., Wu, R., Du, H., Jin, M., Liu, Y., Lei, G., … Tsuchiya, K. (2017). Pneumolysin-dependent calpain activation and interleukin-1α secretion in macrophages infected with Streptococcus pneumoniae. Infection and Immunity, 85(9), e00201-17. doi:10.1128/IAI.00201-17
  • Foletti, D., Strop, P., Shaughnessy, L., Hasa-Moreno, A., Casas, M. G., Russell, M., … Shelton, D. (2013). Mechanism of action and in vivo efficacy of a human-derived antibody against staphylococcus aureus α-hemolysin. Journal of Molecular Biology, 425(10), 1641–1654. doi:10.1016/j.jmb.2013.02.008
  • Gammon, K. (2014). Drug discovery: Leaving no stone unturned. Nature, 509(7498), S10–S12. doi:10.1038/509S10a
  • Ganesan, A., Coote, M. L., & Barakat, K. (2017). Molecular dynamics-driven drug discovery: Leaping forward with confidence. Drug Discovery Today, 22(2), 249–269. doi:10.1016/j.drudis.2016.11.001
  • Giri Rao, V. V. H., Desikan, R., Ayappa, K. G., & Gosavi, S. (2016). Capturing the membrane-triggered conformational transition of an α-helical pore-forming toxin. The Journal of Physical Chemistry B, 120(47), 12064–12078. doi:10.1021/acs.jpcb.6b09400
  • Gouaux, E. (1998). α-hemolysin from staphylococcus aureus: An archetype of β-barrel channel-forming toxins. Journal of Structural Biology, 121(2), 110–122. doi:10.1006/jsbi.1998.3959
  • Gupta, K., Donlan, J. A. C., Hopper, J. T. S., Uzdavinys, P., Landreh, M., Struwe, W. B., … Robinson, C. V. (2017). The role of interfacial lipids in stabilizing membrane protein oligomers. Nature, 541(7637), 421–424. doi:10.1038/nature20820
  • Henry, B. D., Neill, D. R., Becker, K. A., Gore, S., Bricio-Moreno, L., Ziobro, R., … Babiychuk, E. B. (2015). Engineered liposomes sequester bacterial exotoxins and protect from severe invasive infections in mice. Nature Biotechnology, 33(1), 81–88. doi:10.1038/nbt.3037
  • Hess, B., Bekker, H., Berendsen, H. J. C., & Fraaije, J. G. E. M. (1997). LINCS: A linear constraint solver for molecular simulations. Journal of Computational Chemistry, 18(12), 1463–1472. doi:10.1002/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H
  • Hu, C. M., Fang, R. H., Copp, J., Luk, B. T., & Zhang, L. (2013). A biomimetic nanosponge that absorbs pore-forming toxins. Nature Nanotechnology, 8(5), 336–340. doi:10.1038/nnano.2013.54
  • Humphrey, W., Dalke, A., & Schulten, K. (1996). VMD: Visual molecular dynamics. Journal of Molecular Graphics, 14(1), 33–38. doi:10.1016/0263-7855(96)00018-5
  • Jämbeck, J. P. M., & Lyubartsev, A. P. (2012). Derivation and systematic validation of a refined all-atom force field for phosphatidylcholine lipids. The Journal of Physical Chemistry B, 116(10), 3164–3179. doi:10.1021/jp212503e
  • Johnson, S., Brooks, N. J., Smith, R. A., Lea, S. M., & Bubeck, D. (2013). Structural basis for recognition of the pore-forming toxin intermedilysin by human complement receptor CD59. Cell Reports, 3(5), 1369–1377. doi:10.1016/j.celrep.2013.04.029
  • Jorgensen, W. L., Chandrasekhar, J., Madura, J. D., Impey, R. W., & Klein, M. L. (1983). Comparison of simple potential functions for simulating liquid water. The Journal of Chemical Physics, 79(2), 926–935. doi:10.1063/1.445869
  • Karshikoff, A., & Jelesarov, I. (2008). Salt bridges and conformational flexibility: Effect on protein stability. Biotechnology & Biotechnological Equipment, 22(1), 606–611. doi:10.1080/13102818.2008.10817520
  • Krissinel, E., & Henrick, K. (2007). Inference of macromolecular assemblies from crystalline state. Journal of Molecular Biology, 372(3), 774–797. doi:10.1016/j.jmb.2007.05.022
  • Kristan, K. C., Viero, G., Serra, M. D., Macek, P., & Anderluh, G. (2009). Molecular mechanism of pore formation by actinoporins. Toxicon, 54(8), 1125–1134. doi:10.1016/j.toxicon.2009.02.026
  • Kumar, H., Lansac, Y., Glaser, M. A., & Maiti, P. K. (2011). Biopolymers in nanopores: Challenges and opportunities. Soft Matter, 7(13), 5898–5907. doi:10.1039/c0sm01517b
  • Kumar, S., & Nussinov, R. (2002). Close-range electrostatic interactions in proteins. ChemBioChem, 3(7), 604–617. doi:10.1002/1439-7633(20020703)3:7<604::AID-CBIC604>3.0.CO;2-X
  • Kumari, R., Open Source Drug Discovery Consortium, Kumar, R., & Lynn, A. (2014). g_mmpbsa-a – GROMACS tool for high-throughput MM-PBSA calculations. Journal of Chemical Information and Modeling, 54(7), 1951–1962. doi:10.1021/ci500020m
  • Landau, M., Mayrose, I., Rosenberg, Y., Glaser, F., Martz, E., Pupko, T., & Ben-Tal, N. (2005). ConSurf 2005: The projection of evolutionary conservation scores of residues on protein structures. Nucleic Acids Res, 33(Web Server issue), 299–302.
  • Levy, E. D. (2010). A simple definition of structural regions in proteins and its use in analyzing interface evolution. Journal of Molecular Biology, 403(4), 660–670. doi:10.1016/j.jmb.2010.09.028
  • Lindorff-Larsen, K., Piana, S., Palmo, K., Maragakis, P., Klepeis, J. L., Dror, R. O., & Shaw, D. E. (2010). Improved side-chain torsion potentials for the Amber ff99SB protein force field. Proteins: Structure, Function, and Bioinformatics, 78(8), 1950–1958. doi:10.1002/prot.22711
  • Lippow, S. M., Wittrup, K. D., & Tidor, B. (2007). Computational design of antibody-affinity improvement beyond in vivo maturation. Nature Biotechnology, 25(10), 1171–1176. doi:10.1038/nbt1336
  • Lomize, M. A., Pogozheva, I. D., Joo, H., Mosberg, H. I., & Lomize, A. L. (2012). OPM database and PPM web server: Resources for positioning of proteins in membranes. Nucleic Acids Research, 40(D1), D370–376. doi:10.1093/nar/gkr703
  • Los, F. C., Randis, T. M., Aroian, R. V., & Ratner, A. J. (2013). Role of pore-forming toxins in bacterial infectious diseases. Microbiology and Molecular Biology Reviews, 77(2), 173–207. doi:10.1128/MMBR.00052-12
  • Mandal, T., Kanchi, S., Ayappa, K. G., & Maiti, P. K. (2016). pH controlled gating of toxic protein pores by dendrimers. Nanoscale, 8(26), 13045–13058. doi:10.1039/C6NR02963A
  • Menzies, B. E., & Kernodle, D. S. (1994). Site-directed mutagenesis of the alpha-toxin gene of staphylococcus aureus: Role of histidines in toxin activity in vitro and in a murine model. Infection and Immunity, 62(5), 1843–1847. doi:10.1128/IAI.62.5.1843-1847.1994
  • Mesa-Galloso, H., Delgado-Magnero, K. H., Cabezas, S., López-Castilla, A., Hernández-González, J. E., Pedrera, L., … Valiente, P. A. (2017). Disrupting a key hydrophobic pair in the oligomerization interface of the actinoporins impairs their pore-forming activity. Protein Science, 26(3), 550–565. doi:10.1002/pro.3104
  • Mueller, M., Grauschopf, U., Maier, T., Glockshuber, R., & Ban, N. (2009). The structure of a cytolytic α-helical toxin pore reveals its assembly mechanism. Nature, 459(7247), 726–730. doi:10.1038/nature08026
  • Nerenberg, P. S., & Head-Gordon, T. (2011). Optimizing protein-solvent force fields to reproduce intrinsic conformational preferences of model peptides. Journal of Chemical Theory and Computation, 7(4), 1220–1230. doi:10.1021/ct2000183
  • Nestorovich, E. M., & Bezrukov, S. M. (2014). Designing inhibitors of anthrax toxin. Expert Opinion on Drug Discovery, 9(3), 299–318. doi:10.1517/17460441.2014.877884
  • Opal, S. M. (2016). Non-antibiotic treatments for bacterial diseases in an era of progressive antibiotic resistance. Critical Care, 20(1), 397. doi:10.1186/s13054-016-1549-1
  • Panchal, R. G., & Bayley, H. (1995). Interactions between residues in staphylococcal α-hemolysin revealed by reversion mutagenesis. Journal of Biological Chemistry, 270(39), 23072–23076. doi:10.1074/jbc.270.39.23072
  • Park, H., Bradley, P., Greisen, P., Liu, Y., Mulligan, V. K., Kim, D. E., … DiMaio, F. (2016). Simultaneous optimization of biomolecular energy functions on features from small molecules and macromolecules. Journal of Chemical Theory and Computation, 12(12), 6201–6212. doi:10.1021/acs.jctc.6b00819
  • Parker, D., & Prince, A. (2016). A new approach to toxin neutralization in Staphylococcus aureus therapy. EMBO Reports, 17(3), 284–285. doi:10.15252/embr.201642015
  • Parker, M. W., & Feil, S. C. (2005). Pore-forming protein toxins: From structure to function. Progress in Biophysics and Molecular Biology, 88(1), 91–142. doi:10.1016/j.pbiomolbio.2004.01.009
  • Parrinello, M., & Rahman, A. (1981). Polymorphic transitions in single crystals: A new molecular dynamics method. Journal of Applied Physics, 52(12), 7182–7190. doi:10.1063/1.328693
  • Peraro, M. D., & van der Goot, F. G. (2016). Pore-forming toxins: Ancient, but never really out of fashion. Nature Reviews Microbiology, 14(2), 77–92. doi:10.1038/nrmicro.2015.3
  • Phillips, R., Ursell, T., Wiggins, P., & Sens, P. (2009). Emerging roles for lipids in shaping membrane-protein function. Nature, 459(7245), 379–385. doi:10.1038/nature08147
  • Ponmalar, I. I., Cheerla, R., Ayappa, K. G., & Basu, J. K. (2019). Correlated protein conformational states and membrane dynamics during attack by pore-forming toxins. Proceedings of the National Academy of Sciences, 116(26), 12839–12844. doi:10.1073/pnas.1821897116
  • Pronk, S., Páll, S., Schulz, R., Larsson, P., Bjelkmar, P., Apostolov, R., … Lindahl, E. (2013). GROMACS 4.5: A high-throughput and highly parallel open source molecular simulation toolkit. Bioinformatics, 29(7), 845–854. doi:10.1093/bioinformatics/btt055
  • Ragle, B. E., Karginov, V. A., & Bubeck Wardenburg, J. (2010). Prevention and treatment of Staphylococcus aureus pneumonia with a β-cyclodextrin derivative. Antimicrobial Agents and Chemotherapy, 54(1), 298–304. doi:10.1128/AAC.00973-09
  • Rai, P., Padala, C., Poon, V., Saraph, A., Basha, S., Kate, S., … Kane, R. S. (2006). Statistical pattern matching facilitates the design of polyvalent inhibitors of anthrax and cholera toxins. Nature Biotechnology, 24(5), 582–586. doi:10.1038/nbt1204
  • Reyes-Robles, T., Lubkin, A., Alonzo, F., Lacy, D. B., & Torres, V. J. (2016). Exploiting dominant-negative toxins to combat Staphylococcus aureus pathogenesis. EMBO Reports, 17(3), 428–440. doi:10.15252/embr.201540994
  • Rosch, J. W., Boyd, A. R., Hinojosa, E., Pestina, T., Hu, Y., Persons, D. A., … Tuomanen, E. I. (2010). Statins protect against fulminant pneumococcal infection and cytolysin toxicity in a mouse model of sickle cell disease. Journal of Clinical Investigation, 120(2), 627–635. doi:10.1172/JCI39843
  • Rouse, S. L., & Sansom, M. S. P. (2015). Interactions of lipids and detergents with a viral ion channel protein: Molecular dynamics simulation studies. The Journal of Physical Chemistry B, 119(3), 764–772. doi:10.1021/jp505127y
  • Sammalkorpi, M., Karttunen, M., & Haataja, M. (2007). Structural properties of ionic detergent aggregates: A large-scale molecular dynamics study of sodium dodecyl sulfate. The Journal of Physical Chemistry B, 111(40), 11722–11733. doi:10.1021/jp072587a
  • Sathyanarayana, P., Maurya, S., Behera, A., Ravichandran, M., Visweswariah, S. S., Ayappa, K. G., & Roy, R. (2018). Cholesterol promotes cytolysin A activity by stabilizing the intermediates during pore formation. Proceedings of the National Academy of Sciences, 115(31), E7323–E7330. doi:10.1073/pnas.1721228115
  • Soskine, M., Biesemans, A., De Maeyer, M., & Maglia, G. (2013). Tuning the size and properties of ClyA nanopores assisted by directed evolution. Journal of the American Chemical Society, 135(36), 13456–13463. doi:10.1021/ja4053398
  • Soskine, M., Biesemans, A., Moeyaert, B., Cheley, S., Bayley, H., & Maglia, G. (2012). An engineered ClyA nanopore detects folded target proteins by selective external association and pore entry. Nano Letters, 12(9), 4895–4900. doi:10.1021/nl3024438
  • Tanaka, K., Caaveiro, J. M., Morante, K., Gonzalez-Manas, J. M., & Tsumoto, K. (2015). Structural basis for self-assembly of a cytolytic pore lined by protein and lipid. Nature Communications, 6(1), 6337. doi:10.1038/ncomms7337
  • Thompson, J. R., Cronin, B., Bayley, H., & Wallace, M. (2011). Rapid assembly of a multimeric membrane protein pore. Biophysical Journal, 101(11), 2679–2683. doi:10.1016/j.bpj.2011.09.054
  • Tien, M. Z., Meyer, A. G., Sydykova, D. K., Spielman, S. J., & Wilke, C. O. (2013). Maximum allowed solvent accessibilites of residues in proteins. PLoS One, 8(11), e80635. doi:10.1371/journal.pone.0080635
  • Tkaczyk, C., Hamilton, M. M., Sadowska, A., Shi, Y., Chang, C. S., Chowdhury, P., … Sellman, B. R. (2016). Targeting alpha toxin and ClfA with a multimechanistic monoclonal-antibody-based approach for prophylaxis of serious Staphylococcus aureus disease. mBio, 7(3), e00528-16. doi:10.1128/mBio.00528-16
  • Tzokov, S. B., Wyborn, N. R., Stillman, T. J., Jamieson, S., Czudnochowski, N., Artymiuk, P. J., … Bullough, P. A. (2006). Structure of the hemolysin E (HlyE, ClyA, and SheA) channel in its membrane-bound form. The Journal of Biological Chemistry, 281(32), 23042–23049. doi:10.1074/jbc.M602421200
  • Vogele, M., Bhaskara, R. M., Mulvihill, E., van Pee, K., Yildiz, O., Kuhlbrandt, W., …Hummer, G. (2019). Membrane perforation by the pore-forming toxin pneumolysin. Proceedings of the National Academy of Sciences, 116(27), 13352–13357. doi:10.1073/pnas.1904304116
  • Wade, K. R., Hotze, E. M., Kuiper, M. J., Morton, C. J., Parker, M. W., & Tweten, R. K. (2015). An intermolecular electrostatic interaction controls the prepore-to-pore transition in a cholesterol-dependent cytolysin. Proceedings of the National Academy of Sciences, 112(7), 2204–2209. doi:10.1073/pnas.1423754112
  • Waldburger, C. D., Schildbach, J. F., & Sauer, R. T. (1995). Are buried salt bridges important for protein stability and conformational specificity? Nature Structural & Molecular Biology, 2(2), 122–128. doi:10.1038/nsb0295-122
  • Walker, B., & Bayley, H. (1995a). Key residues for membrane binding, oligomerization, and pore forming activity of staphylococcal alpha-hemolysin identified by cysteine scanning mutagenesis and targeted chemical modification. Journal of Biological Chemistry, 270(39), 23065–23071. doi:10.1074/jbc.270.39.23065
  • Walker, B., & Bayley, H. (1995b). Restoration of pore-forming activity in staphylococcal α-hemolysin by targeted covalent modification. Protein Engineering, Design and Selection, 8(5), 491–495. doi:10.1093/protein/8.5.491
  • Wei, X., Gao, J., Wang, F., Ying, M., Angsantikul, P., Kroll, A. V., … Zhang, L. (2017). In situ capture of bacterial toxins for antivirulence vaccination. Advanced Materials, 29(33), 1701644. doi:10.1002/adma.201701644
  • Woolfson, D. N., Bartlett, G. J., Bruning, M., & Thomson, A. R. (2012). New currency for old rope: From coiled-coil assemblies to α-helical barrels. Current Opinion in Structural Biology, 22(4), 432–441. doi:10.1016/j.sbi.2012.03.002
  • Worth, C. L., & Blundell, T. L. (2010). On the evolutionary conservation of hydrogen bonds made by buried polar amino acids: The hidden joists, braces and trusses of protein architecture. BMC Evolutionary Biology, 10(1), 161. doi:10.1186/1471-2148-10-161
  • Yilmaz, N., & Kobayashi, T. (2015). Visualization of lipid membrane reorganization induced by a pore-forming toxin using high-speed atomic force microscopy. ACS Nano, 9(8), 7960–7967. doi:10.1021/acsnano.5b01041
  • Zafar, M. A., Wang, Y., Hamaguchi, S., & Weiser, J. N. (2017). Host-to-host transmission of Streptococcus pneumoniae is driven by its inflammatory toxin, pneumolysin. Cell Host Microbe, 21(1), 73–83. doi:10.1016/j.chom.2016.12.005

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.