1932

Abstract

Cooperativity (homotropic allostery) is the primary mechanism by which evolution steepens the binding curves of biomolecular receptors to produce more responsive input–output behavior in biomolecular systems. Motivated by the ubiquity with which nature employs this effect, over the past 15 years we, together with other groups, have engineered this mechanism into several otherwise noncooperative receptors. These efforts largely aimed to improve the utility of such receptors in artificial biotechnologies, such as synthetic biology and biosensors, but they have also provided the first quantitative, experimental tests of longstanding ideas about the mechanisms underlying cooperativity. In this article, we review the literature on the design of this effect, paying particular attention to the design strategies involved, the extent to which each can be rationally applied to (and optimized for) new receptors, and what each teaches us about the origins and optimization of this important phenomenon.

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2023-05-09
2024-04-13
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Literature Cited

  1. 1.
    Ackers GK, Doyle ML, Myers D, Daugherty MA. 1992. Molecular code for cooperativity in hemoglobin. Science 255:54–63
    [Google Scholar]
  2. 2.
    Arroyo-Currás N, Dauphin-Ducharme P, Scida K, Chávez JL. 2020. From the beaker to the body: translational challenges for electrochemical, aptamer-based sensors. Anal. Methods 12:1288–310
    [Google Scholar]
  3. 3.
    Arshad U, Taubert M, Seeger-Nukpezah T, Ullah S, Spindeldreier KC et al. 2021. Evaluation of body-surface-area adjusted dosing of high-dose methotrexate by population pharmacokinetics in a large cohort of cancer patients. BMC Cancer 21:719
    [Google Scholar]
  4. 4.
    Barcroft J, Roberts F. 1909. The dissociation curve of haemoglobin. J. Physiol. 39:143–48
    [Google Scholar]
  5. 5.
    Bernardo-Seisdedos G, Nunez E, Gomis-Perez C, Malo C, Villarroel A, Millet O. 2018. Structural basis and energy landscape for the Ca2+ gating and calmodulation of the Kv7.2 K+ channel. PNAS 115:2395–400
    [Google Scholar]
  6. 6.
    Bisswanger H. 1984. Cooperativity in highly aggregated enzyme systems. A slow transition model for the pyruvate dehydrogenase complex from Escherichia coli. J. Biol. Chem. 259:2457–65
    [Google Scholar]
  7. 7.
    Bohr C, Hasselbalch K, Krogh A. 1904. Ueber einen in biologischer Beziehung wichtigen Einfluss, den die Kohlensäurespannung des Blutes auf dessen Sauerstoffbindung übt. Skand. Arch. Physiol. 16:402–12
    [Google Scholar]
  8. 8.
    Bristow CC, Severe L, Pape JW, Javanbakht M, Lee S-J et al. 2016. Dual rapid lateral flow immunoassay fingerstick wholeblood testing for syphilis and HIV infections is acceptable and accurate, Port-au-Prince, Haiti. BMC Infect. Dis. 16:302
    [Google Scholar]
  9. 9.
    Brunori M. 2014. Variations on the theme: allosteric control in hemoglobin. FEBS J. 281:633–43
    [Google Scholar]
  10. 10.
    Chan HS, Dill KA. 1989. Intrachain loops in polymers: effects of excluded volume. J. Chem. Phys. 90:492–509
    [Google Scholar]
  11. 11.
    Colquhoun D. 2006. The quantitative analysis of drug-receptor interactions: a short history. Trends Pharmacol. Sci. 27:149–57
    [Google Scholar]
  12. 12.
    Cordeiro TN, Sibille N, Germain P, Barthe P, Boulahtouf A et al. 2019. Interplay of protein disorder in retinoic acid receptor heterodimer and its corepressor regulates gene expression. Structure 27:1270–85.e6
    [Google Scholar]
  13. 13.
    Corn R. 2005. Enzymatically amplified SPR imaging for biosensor microarrays: fighting the tyranny of the Langmuir isotherm. Abstr. Pap. Am. Chem. Soc. 230:U330–31
    [Google Scholar]
  14. 14.
    Dueber JE, Mirsky EA, Lim WA. 2007. Engineering synthetic signaling proteins with ultrasensitive input/output control. Nat. Biotechnol. 25:660–62
    [Google Scholar]
  15. 15.
    Ellington AD, Szostak JW. 1990. In vitro selection of RNA molecules that bind specific ligands. Nature 346:818–22
    [Google Scholar]
  16. 16.
    Ferrell JE Jr. 2009. Q&A: Cooperativity. J. Biol. 8:53
    [Google Scholar]
  17. 17.
    Ferriere F, Khan NA, Meyniel JP, Deschaux P. 1999. Characterisation of serotonin transport mechanisms in rainbow trout peripheral blood lymphocytes: role in PHA-induced lymphoproliferation. Dev. Comp. Immunol. 23:37–50
    [Google Scholar]
  18. 18.
    Goldbeter A. 1976. On the role of enzyme cooperativity in metabolic oscillations: analysis of the hill coefficient in a model for glycolytic periodicities. Biophys. Chem. 6:95–99
    [Google Scholar]
  19. 19.
    Hill AV. 1909. The mode of action of nicotine and curari, determined by the form of the contraction curve and the method of temperature coefficients. J. Physiol. 39:361–73
    [Google Scholar]
  20. 20.
    Hill AV. 1910. The possible effects of the aggregation of the molecules of hemoglobin on its dissociation curves. J. Physiol. 40:iv–vii
    [Google Scholar]
  21. 21.
    Ismail SI, Alshaer W. 2018. Therapeutic aptamers in discovery, preclinical and clinical stages. Adv. Drug Deliv. Rev. 134:51–64
    [Google Scholar]
  22. 22.
    Kang D, Vallée-Bélisle A, Porchetta A, Plaxco KW, Ricci F. 2012. Re-engineering electrochemical biosensors to narrow or extend their useful dynamic range. Angew. Chem. Int. Ed. Engl. 51:6717–21
    [Google Scholar]
  23. 23.
    Koshland DE, Hamadani K. 2002. Proteomics and models for enzyme cooperativity. J. Biol. Chem. 277:46841–44
    [Google Scholar]
  24. 24.
    Krell T, Teran W, Mayorga OL, Rivas G, Jimenez M et al. 2007. Optimization of the palindromic order of the TtgR operator enhances binding cooperativity. J. Mol. Biol. 369:1188–99
    [Google Scholar]
  25. 25.
    Langmuir I. 1916. The constitution and fundamental properties of solids and liquids. Part I. Solids. J. Am. Chem. Soc. 38:2221–95
    [Google Scholar]
  26. 26.
    Lee AW, Karplus M. 1983. Structure-specific model of hemoglobin cooperativity. PNAS 80:7055–59
    [Google Scholar]
  27. 27.
    Leonard RCF, Williams S, Tulpule A, Levine AM, Oliveros S. 2009. Improving the therapeutic index of anthracycline chemotherapy: focus on liposomal doxorubicin (Myocet™). Breast 18:218–24
    [Google Scholar]
  28. 28.
    Li H, Somerson J, Xia F, Plaxco KW. 2018. Electrochemical DNA-based sensors for molecular quality control: continuous, real-time melamine detection in flowing whole milk. Anal. Chem. 90:10641–45
    [Google Scholar]
  29. 29.
    Linse S, Chazin WJ. 1995. Quantitative measurements of the cooperativity in an EF-hand protein with sequential calcium binding. Protein Sci. 4:1038–44
    [Google Scholar]
  30. 30.
    Liu J, Nussinov R. 2016. Allostery: an overview of its history, concepts, methods, and applications. PLOS Comput. Biol. 12:e1004966
    [Google Scholar]
  31. 31.
    Luo Y, Yu H, Alkhamis O, Liu Y, Lou X et al. 2019. Label-free, visual detection of small molecules using highly target-responsive multimodule split aptamer constructs. Anal. Chem. 91:7199–207
    [Google Scholar]
  32. 32.
    Mariottini D, Idili A, Vallée-Bélisle A, Plaxco KW, Ricci F. 2017. A DNA nanodevice that loads and releases a cargo with hemoglobin-like allosteric control and cooperativity. Nano Lett. 17:3225–30
    [Google Scholar]
  33. 33.
    Mendels D-A, Dortet L, Emeraud C, Oueslati S, Girlich D et al. 2021. Using artificial intelligence to improve COVID-19 rapid diagnostic test result interpretation. PNAS 118:e2019893118
    [Google Scholar]
  34. 34.
    Meyer T, Holowka D, Stryer L. 1988. Highly cooperative opening of calcium channels by inositol 1,4,5-trisphosphate. Science 240:653–56
    [Google Scholar]
  35. 35.
    Monod J, Jacob F 1961. Teleonomic mechanisms in cellular metabolism, growth, and differentiation. Cold Spring Harb. Symp. Quant. Biol. 26:389–401
    [Google Scholar]
  36. 36.
    Monod J, Wyman J, Changeux J-P. 1965. On the nature of allosteric transitions: a plausible model. J. Mol. Biol. 12:88–118
    [Google Scholar]
  37. 37.
    Mullen MA, Assmann SM, Bevilacqua PC. 2012. Toward a digital gene response: RNA G-quadruplexes with fewer quartets fold with higher cooperativity. J. Am. Chem. Soc. 134:812–15
    [Google Scholar]
  38. 38.
    Nesterova IV, Briscoe JR, Nesterov EE. 2015. Rational control of folding cooperativity in DNA quadruplexes. J. Am. Chem. Soc. 137:11234–37
    [Google Scholar]
  39. 39.
    Notides AC, Lerner N, Hamilton DE. 1981. Positive cooperativity of the estrogen receptor. PNAS 78:4926–30
    [Google Scholar]
  40. 40.
    Ortega G, Mariottini D, Troina A, Dahlquist FW, Ricci F, Plaxco KW. 2020. Rational design to control the trade-off between receptor affinity and cooperativity. PNAS 117:19136–40
    [Google Scholar]
  41. 41.
    Paner TM, Amaratunga M, Benight AS. 1992. Studies of DNA dumbbells. III. Theoretical analysis of optical melting curves of dumbbells with a 16 base-pair duplex stem and Tn end loops (n = 2, 3, 4, 6, 8, 10, 14). Biopolymers 32:881–92
    [Google Scholar]
  42. 42.
    Peselis A, Gao A, Serganov A. 2015. Cooperativity, allostery and synergism in ligand binding to riboswitches. Biochimie 117:100–9
    [Google Scholar]
  43. 43.
    Ricci F, Vallee-Belisle A, Simon AJ, Porchetta A, Plaxco KW. 2016. Using nature's “tricks” to rationally tune the binding properties of biomolecular receptors. Acc. Chem. Res. 49:1884–92
    [Google Scholar]
  44. 44.
    Roy M, Horovitz A. 2022. Partitioning the Hill coefficient into contributions from ligand-promoted conformational changes and subunit heterogeneity. Protein Sci. 31:e4298
    [Google Scholar]
  45. 45.
    Sena-Torralba A, Torné-Morató H, Parolo C, Ranjbar S, Farahmand Nejad MA et al. 2022. A novel ratiometric fluorescent approach for the modulation of the dynamic range of lateral flow immunoassays. Adv. Mater. Technol. 7:2101450
    [Google Scholar]
  46. 46.
    Sharon M, Horovitz A. 2015. Probing allosteric mechanisms using native mass spectrometry. Curr. Opin. Struct. Biol. 34:7–16
    [Google Scholar]
  47. 47.
    Simon AJ, Vallee-Belisle A, Ricci F, Plaxco KW. 2014. Intrinsic disorder as a generalizable strategy for the rational design of highly responsive, allosterically cooperative receptors. PNAS 111:15048–53
    [Google Scholar]
  48. 48.
    Simon AJ, Vallee-Belisle A, Ricci F, Watkins HM, Plaxco KW. 2014. Using the population-shift mechanism to rationally introduce “Hill-type” cooperativity into a normally non-cooperative receptor. Angew. Chem. Int. Ed. Engl. 53:9471–75
    [Google Scholar]
  49. 49.
    Tuerk C, Gold L. 1990. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249:505–10
    [Google Scholar]
  50. 50.
    Tyagi S, Kramer FR. 1996. Molecular beacons: probes that fluoresce upon hybridization. Nat. Biotechnol. 14:303–8
    [Google Scholar]
  51. 51.
    Undevia SD, Gomez-Abuin G, Ratain MJ. 2005. Pharmacokinetic variability of anticancer agents. Nat. Rev. Cancer 5:447–58
    [Google Scholar]
  52. 52.
    Walling J. 2006. From methotrexate to pemetrexed and beyond. A review of the pharmacodynamic and clinical properties of antifolates. Investig. New Drugs 24:37–77
    [Google Scholar]
  53. 53.
    Wang Z, Heon Lee J, Lu Y 2008. Highly sensitive “turn-on” fluorescent sensor for Hg2+ in aqueous solution based on structure-switching DNA. Chem. Commun. 45:6005–7
    [Google Scholar]
  54. 54.
    Whitty A. 2008. Cooperativity and biological complexity. Nat. Chem. Biol. 4:435–39
    [Google Scholar]
  55. 55.
    World Health Organ 2002. HIV simple/rapid assays: operational characteristics (Phase I). Report 12: simple rapid tests, whole blood specimens Rep. WHO/BCT/02.07 World Health Organ. Geneva:
  56. 56.
    Yu H, Canoura J, Guntupalli B, Alkhamis O, Xiao Y 2018. Sensitive detection of small-molecule targets using cooperative binding split aptamers and enzyme-assisted target recycling. Anal. Chem. 90:1748–58
    [Google Scholar]
  57. 57.
    Yu H, Canoura J, Guntupalli B, Lou X, Xiao Y. 2017. A cooperative-binding split aptamer assay for rapid, specific and ultra-sensitive fluorescence detection of cocaine in saliva. Chem. Sci. 8:131–41
    [Google Scholar]
  58. 58.
    Zhang Q, Bhattacharya S, Andersen ME. 2013. Ultrasensitive response motifs: basic amplifiers in molecular signalling networks. Open Biol. 3:130031
    [Google Scholar]
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