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Current Protein & Peptide Science

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ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

Review Article

Ligand-Linked Association-Dissociation in Transport Proteins and Hormone Receptors

Author(s): ">Fulvio Saccoccia and Andrea Bellelli*

Volume 21, Issue 10, 2020

Page: [993 - 1010] Pages: 18

DOI: 10.2174/1389203721666200810143300

Price: $65

Abstract

Ligand-linked changes in the aggregation state of biological macromolecules occur and have importance in several physiological processes, e.g., the response of hormone receptors, cooperative ligand binding, and others. The mathematical formalisms that express the thermodynamics governing these processes are complex, as they are required to describe observations made under experimental conditions in which many parameters may be simultaneously varied. The description of the functional behaviour of proteins that present ligand-linked association-dissociation events must accommodate cases where both the binding stoichiometries and reaction mechanisms are variable. In this paper, we review some paradigmatic cases that cover different structural arrangements and binding modes, with special attention to the case of dissociating homodimeric transport proteins and receptors. Even though we cannot pretend to be comprehensive on the proteins presenting this behaviour, we believe that we can attempt to be comprehensive on the structural arrangements and thermodynamic properties of these systems, which fall into a limited set of possible types.

Keywords: Ligand-linked, association-dissociation, linkage, receptors, hormones, transporter, hemoglobin, cooperativity.

Graphical Abstract

[1]
Fretto, L.J.; Snape, A.J.; Tomlinson, J.E.; Seroogy, J.J.; Wolf, D.L.; LaRochelle, W.J.; Giese, N.A. Mechanism of platelet-derived growth factor (PDGF) AA, AB, and BB binding to alpha and beta PDGF receptor. J. Biol. Chem., 1993, 268(5), 3625-3631.
[PMID: 7679113]
[2]
Ferguson, K.M.; Berger, M.B.; Mendrola, J.M.; Cho, H.S.; Leahy, D.J.; Lemmon, M.A. EGF activates its receptor by removing interactions that autoinhibit ectodomain dimerization. Mol. Cell, 2003, 11(2), 507-517.
[http://dx.doi.org/10.1016/S1097-2765(03)00047-9] [PMID: 12620237]
[3]
Lian, F.M.; Yu, J.; Ma, X.X.; Yu, X.J.; Chen, Y.; Zhou, C.Z. Structural snapshots of yeast alkyl hydroperoxide reductase Ahp1 peroxiredoxin reveal a novel two-cysteine mechanism of electron transfer to eliminate reactive oxygen species. J. Biol. Chem., 2012, 287(21), 17077-17087.
[http://dx.doi.org/10.1074/jbc.M112.357368] [PMID: 22474296]
[4]
Ruch, C.; Skiniotis, G.; Steinmetz, M.O.; Walz, T.; Ballmer-Hofer, K. Structure of a VEGF-VEGF receptor complex determined by electron microscopy. Nat. Struct. Mol. Biol., 2007, 14(3), 249-250.
[http://dx.doi.org/10.1038/nsmb1202] [PMID: 17293873]
[5]
Wells, J.A. Binding in the growth hormone receptor complex. Proc. Natl. Acad. Sci. USA, 1996, 93(1), 1-6.
[http://dx.doi.org/10.1073/pnas.93.1.1] [PMID: 8552582]
[6]
Syed, R.S.; Reid, S.W.; Li, C.; Cheetham, J.C.; Aoki, K.H.; Liu, B.; Zhan, H.; Osslund, T.D.; Chirino, A.J.; Zhang, J.; Finer-Moore, J.; Elliott, S.; Sitney, K.; Katz, B.A.; Matthews, D.J.; Wendoloski, J.J.; Egrie, J.; Stroud, R.M. Efficiency of signalling through cytokine receptors depends critically on receptor orientation. Nature, 1998, 395(6701), 511-516.
[http://dx.doi.org/10.1038/26773] [PMID: 9774108]
[7]
Arnone, A. X-ray diffraction study of binding of 2,3-diphosphoglycerate to human deoxyhaemoglobin. Nature, 1972, 237(5351), 146-149.
[http://dx.doi.org/10.1038/237146a0] [PMID: 4555506]
[8]
Bellelli, A.; Carey, J. Reversible Ligand Binding; Wiley & Sons: New York, 2018.
[9]
Lemmon, M.A.; Bu, Z.; Ladbury, J.E.; Zhou, M.; Pinchasi, D.; Lax, I.; Engelman, D.M.; Schlessinger, J. Two EGF molecules contribute additively to stabilization of the EGFR dimer. EMBO J., 1997, 16(2), 281-294.
[http://dx.doi.org/10.1093/emboj/16.2.281] [PMID: 9029149]
[10]
Mills, F.C.; Ackers, G.K. Quaternary enhancement in binding of oxygen by human hemoglobin. Proc. Natl. Acad. Sci. USA, 1979, 76(1), 273-277.
[http://dx.doi.org/10.1073/pnas.76.1.273] [PMID: 284341]
[11]
Bell, G.I. Models for the specific adhesion of cells to cells. Science, 1978, 200(4342), 618-627.
[http://dx.doi.org/10.1126/science.347575] [PMID: 347575]
[12]
Bell, G.I.; Dembo, M.; Bongrand, P. Cell adhesion. Competition between nonspecific repulsion and specific bonding. Biophys. J., 1984, 45(6), 1051-1064.
[http://dx.doi.org/10.1016/S0006-3495(84)84252-6] [PMID: 6743742]
[13]
Chadda, R.; Cliff, L.; Brimberry, M.; Robertson, J.L. A model-free method for measuring dimerization free energies of CLC-ec1 in lipid bilayers. J. Gen. Physiol., 2018, 150(2), 355-365.
[http://dx.doi.org/10.1085/jgp.201711893] [PMID: 29321261]
[14]
Chen, Sy.; Wang, J.; Yu, Gq.; Liu, W.; Pearce, D. Androgen and glucocorticoid receptor heterodimer formation. A possible mechanism for mutual inhibition of transcriptional activity. J. Biol. Chem., 1997, 272(22), 14087-14092.
[http://dx.doi.org/10.1074/jbc.272.22.14087] [PMID: 9162033]
[15]
Yarden, Y.; Schlessinger, J. Epidermal growth factor induces rapid, reversible aggregation of the purified epidermal growth factor receptor. Biochemistry, 1987, 26(5), 1443-1451.
[http://dx.doi.org/10.1021/bi00379a035] [PMID: 3494473]
[16]
Bello, M. Portillo-Téllez, Mdel.C.; García-Hernández, E. Energetics of ligand recognition and self-association of bovine β-lactoglobulin: differences between variants A and B. Biochemistry, 2011, 50(1), 151-161.
[http://dx.doi.org/10.1021/bi1016155] [PMID: 21117642]
[17]
Fung, J.J.; Deupi, X.; Pardo, L.; Yao, X.J.; Velez-Ruiz, G.A.; Devree, B.T.; Sunahara, R.K.; Kobilka, B.K. Ligand-regulated oligomerization of beta(2)-adrenoceptors in a model lipid bilayer. EMBO J., 2009, 28(21), 3315-3328.
[http://dx.doi.org/10.1038/emboj.2009.267] [PMID: 19763081]
[18]
Doyle, M.L.; Gill, S.J.; Cusanovich, M.A. Ligand-controlled dissociation of Chromatium vinosum cytochrome c′. Biochemistry, 1986, 25(9), 2509-2516.
[http://dx.doi.org/10.1021/bi00357a034] [PMID: 3013306]
[19]
Condon, P.J.; Royer, W.E. Jr Crystal structure of oxygenated Scapharca dimeric hemoglobin at 1.7-A resolution. J. Biol. Chem., 1994, 269(41), 25259-25267.
[PMID: 7929217]
[20]
Royer, W.E., Jr; Fox, R.A.; Smith, F.R.; Zhu, D.; Braswell, E.H. Ligand linked assembly of Scapharca dimeric hemoglobin. J. Biol. Chem., 1997, 272(9), 5689-5694.
[http://dx.doi.org/10.1074/jbc.272.9.5689] [PMID: 9038179]
[21]
Ikeda-Saito, M.; Yonetani, T.; Chiancone, E.; Ascoli, F.; Verzili, D.; Antonini, E. Thermodynamic properties of oxygen equilibria of dimeric and tetrameric hemoglobins from Scapharca inaequivalvis. J. Mol. Biol., 1983, 170(4), 1009-1018.
[http://dx.doi.org/10.1016/S0022-2836(83)80200-9] [PMID: 6644811]
[22]
Andersen, M.E. Sedimentation equilibriujm experiments on the self-assocation of hemoglobin from the lamprey Petromyzon marinus. A model for oxygen transport in the lamprey. J. Biol. Chem., 1971, 246(15), 4800-4806.
[PMID: 5562359]
[23]
Andersen, M.E.; Gibson, Q.H. A kinetic analysis of the binding of oxygen and carbon monoxide to lamprey hemoglobin. Petromyzon marinus and Petromyzon fluviatilis. J. Biol. Chem., 1971, 246(15), 4790-4799.
[PMID: 5562358]
[24]
Heaslet, H.A.; Royer, W.E., Jr Crystalline ligand transitions in lamprey hemoglobin. Structural evidence for the regulation of oxygen affinity. J. Biol. Chem., 2001, 276(28), 26230-26236.
[http://dx.doi.org/10.1074/jbc.M101391200] [PMID: 11340069]
[25]
Qiu, Y.; Maillett, D.H.; Knapp, J.; Olson, J.S.; Riggs, A.F. Lamprey hemoglobin. Structural basis of the bohr effect. J. Biol. Chem., 2000, 275(18), 13517-13528.
[http://dx.doi.org/10.1074/jbc.275.18.13517] [PMID: 10788466]
[26]
Perutz, M.F. Regulation of oxygen affinity of hemoglobin: influence of structure of the globin on the heme iron. Annu. Rev. Biochem., 1979, 48, 327-386.
[http://dx.doi.org/10.1146/annurev.bi.48.070179.001551] [PMID: 382987]
[27]
Gutiérrez-Magdaleno, G.; Bello, M.; Portillo-Téllez, M.C.; Rodríguez-Romero, A.; García-Hernández, E. Ligand binding and self-association cooperativity of β-lactoglobulin. J. Mol. Recognit., 2013, 26(2), 67-75.
[http://dx.doi.org/10.1002/jmr.2249] [PMID: 23334914]
[28]
Horan, T.P.; Martin, F.; Simonet, L.; Arakawa, T.; Philo, J.S. Dimerization of granulocyte-colony stimulating factor receptor: the Ig plus CRH construct of granulocyte-colony stimulating factor receptor forms a 2:2 complex with a ligand. J. Biochem., 1997, 121(2), 370-375.
[http://dx.doi.org/10.1093/oxfordjournals.jbchem.a021597] [PMID: 9089414]
[29]
Freed, D.M.; Alvarado, D.; Lemmon, M.A. Ligand regulation of a constitutively dimeric EGF receptor. Nat. Commun., 2015, 6, 7380.
[http://dx.doi.org/10.1038/ncomms8380] [PMID: 26060020]
[30]
Bessman, N.J.; Bagchi, A.; Ferguson, K.M.; Lemmon, M.A. Complex relationship between ligand binding and dimerization in the epidermal growth factor receptor. Cell Rep., 2014, 9(4), 1306-1317.
[http://dx.doi.org/10.1016/j.celrep.2014.10.010] [PMID: 25453753]
[31]
Savory, J.G.; Préfontaine, G.G.; Lamprecht, C.; Liao, M.; Walther, R.F.; Lefebvre, Y.A.; Haché, R.J. Glucocorticoid receptor homodimers and glucocorticoid-mineralocorticoid receptor heterodimers form in the cytoplasm through alternative dimerization interfaces. Mol. Cell. Biol., 2001, 21(3), 781-793.
[http://dx.doi.org/10.1128/MCB.21.3.781-793.2001] [PMID: 11154266]
[32]
Nixon, M.; Andrew, R.; Chapman, K.E. It takes two to tango: dimerisation of glucocorticoid receptor and its anti-inflammatory functions. Steroids, 2013, 78(1), 59-68.
[http://dx.doi.org/10.1016/j.steroids.2012.09.013] [PMID: 23127816]
[33]
Biggadike, K.; Bledsoe, R.K.; Hassell, A.M.; Kirk, B.E.; McLay, I.M.; Shewchuk, L.M.; Stewart, E.L. X-ray crystal structure of the novel enhanced-affinity glucocorticoid agonist fluticasone furoate in the glucocorticoid receptor-ligand binding domain. J. Med. Chem., 2008, 51(12), 3349-3352.
[http://dx.doi.org/10.1021/jm800279t] [PMID: 18522385]
[34]
Cunningham, B.C.; Ultsch, M.; De Vos, A.M.; Mulkerrin, M.G.; Clauser, K.R.; Wells, J.A. Dimerization of the extracellular domain of the human growth hormone receptor by a single hormone molecule. Science, 1991, 254(5033), 821-825.
[http://dx.doi.org/10.1126/science.1948064] [PMID: 1948064]
[35]
Philo, J.S.; Aoki, K.H.; Arakawa, T.; Narhi, L.O.; Wen, J. Dimerization of the extracellular domain of the erythropoietin (EPO) receptor by EPO: one high-affinity and one low-affinity interaction. Biochemistry, 1996, 35(5), 1681-1691.
[http://dx.doi.org/10.1021/bi9524272] [PMID: 8634300]
[36]
Heldin, C.H.; Ernlund, A.; Rorsman, C.; Rönnstrand, L. Dimerization of B-type platelet-derived growth factor receptors occurs after ligand binding and is closely associated with receptor kinase activation. J. Biol. Chem., 1989, 264(15), 8905-8912.
[PMID: 2542295]
[37]
Benesch, R.E.; Benesch, R.; Kwong, S.; McCord, J.M. Binding of diphosphoglycerate and ATP to oxyhemoglobin dimers. J. Mol. Biol., 1986, 190(3), 481-485.
[http://dx.doi.org/10.1016/0022-2836(86)90016-1] [PMID: 3783709]
[38]
Clackson, T.; Wells, J.A. A hot spot of binding energy in a hormone-receptor interface. Science, 1995, 267(5196), 383-386.
[http://dx.doi.org/10.1126/science.7529940] [PMID: 7529940]
[39]
Pearce, K.H., Jr; Cunningham, B.C.; Fuh, G.; Teeri, T.; Wells, J.A. Growth hormone binding affinity for its receptor surpasses the requirements for cellular activity. Biochemistry, 1999, 38(1), 81-89.
[http://dx.doi.org/10.1021/bi9817008] [PMID: 9890885]
[40]
Grünewald, F.S.; Prota, A.E.; Giese, A.; Ballmer-Hofer, K. Structure-function analysis of VEGF receptor activation and the role of coreceptors in angiogenic signaling. Biochim. Biophys. Acta, 2010, 1804(3), 567-580.
[http://dx.doi.org/10.1016/j.bbapap.2009.09.002] [PMID: 19761875]
[41]
Huang, Y.; Doyle, M.L.; Ackers, G.K. The oxygen-binding intermediates of human hemoglobin: evaluation of their contributions to cooperativity using zinc-containing hybrids. Biophys. J., 1996, 71(4), 2094-2105.
[http://dx.doi.org/10.1016/S0006-3495(96)79408-0] [PMID: 8889184]
[42]
Auriau, J.; Roujeau, C.; Belaid Choucair, Z.; Oishi, A.; Derviaux, C.; Roux, T.; Trinquet, E.; Hermine, O.; Jockers, R.; Dam, J. Gain of affinity for VEGF165 binding within the VEGFR2/NRP1 cellular complex detected by an HTRF-based binding assay. Biochem. Pharmacol., 2018, 158, 45-59.
[http://dx.doi.org/10.1016/j.bcp.2018.09.014] [PMID: 30236477]
[43]
Walter, M.R.; Nagabhushan, T.L. Crystal structure of interleukin 10 reveals an interferon gamma-like fold. Biochemistry, 1995, 34(38), 12118-12125.
[http://dx.doi.org/10.1021/bi00038a004] [PMID: 7547951]
[44]
Banner, D.W.; D’Arcy, A.; Janes, W.; Gentz, R.; Schoenfeld, H.J.; Broger, C.; Loetscher, H.; Lesslauer, W. Crystal structure of the soluble human 55 kd TNF receptor-human TNF beta complex: implications for TNF receptor activation. Cell, 1993, 73(3), 431-445.
[http://dx.doi.org/10.1016/0092-8674(93)90132-A] [PMID: 8387891]
[45]
Mrabet, N.T.; Shaeffer, J.R.; McDonald, M.J.; Bunn, H.F. Dissociation of dimers of human hemoglobins A and F into monomers. J. Biol. Chem., 1986, 261(3), 1111-1115.
[PMID: 2418013]
[46]
Edelstein, S.J.; Rehmar, M.J.; Olson, J.S.; Gibson, Q.H. Functional aspects of the subunit association-dissociation equilibria of hemoglobin. J. Biol. Chem., 1970, 245(17), 4372-4381.
[PMID: 5498425]
[47]
Thomas, J.O.; Edelstein, S.J. Observation of the dissociation of unliganded hemoglobin. J. Biol. Chem., 1972, 247(24), 7870-7874.
[PMID: 4640927]
[48]
Tripathi, T.; Rahlfs, S.; Becker, K.; Bhakuni, V. Glutathione mediated regulation of oligomeric structure and functional activity of Plasmodium falciparum glutathione S-transferase. BMC Struct. Biol., 2007, 7, 67.
[http://dx.doi.org/10.1186/1472-6807-7-67] [PMID: 17941979]
[49]
Foss, T.R.; Wiseman, R.L.; Kelly, J.W. The pathway by which the tetrameric protein transthyretin dissociates. Biochemistry, 2005, 44(47), 15525-15533.
[http://dx.doi.org/10.1021/bi051608t] [PMID: 16300401]
[50]
Barry, J.K.; Matthews, K.S. Thermodynamic analysis of unfolding and dissociation in lactose repressor protein. Biochemistry, 1999, 38(20), 6520-6528.
[http://dx.doi.org/10.1021/bi9900727] [PMID: 10350470]
[51]
Monod, J.; Wyman, J.; Changeux, J.P. On the nature of allosteric transitions. A plausible model. J. Mol. Biol., 1965, 12, 88-118.
[http://dx.doi.org/10.1016/S0022-2836(65)80285-6] [PMID: 14343300]
[52]
Dickerson, R.E.; Geis, I. Hemoglobin; Benjamin Cummings: Menlo Park, CA, USA, 1983.
[53]
Perutz, M.F. Stereochemistry of cooperative effects in haemoglobin. Nature, 1970, 228(5273), 726-739.
[http://dx.doi.org/10.1038/228726a0] [PMID: 5528785]
[54]
Baldwin, J.; Chothia, C. Haemoglobin: the structural changes related to ligand binding and its allosteric mechanism. J. Mol. Biol., 1979, 129(2), 175-220.
[http://dx.doi.org/10.1016/0022-2836(79)90277-8] [PMID: 39173]
[55]
Angelucci, F.; Bellelli, A.; Ardini, M.; Ippoliti, R.; Saccoccia, F.; Morea, V. One ring (or two) to hold them all – on the structure and function of protein nanotubes. FEBS J., 2015, 282(15), 2827-2845.
[http://dx.doi.org/10.1111/febs.13336] [PMID: 26059483]
[56]
Lesk, A.M.; Janin, J.; Wodak, S.; Chothia, C. Haemoglobin: the surface buried between the alpha 1 beta 1 and alpha 2 beta 2 dimers in the deoxy and oxy structures. J. Mol. Biol., 1985, 183(2), 267-270.
[http://dx.doi.org/10.1016/0022-2836(85)90219-0] [PMID: 4009726]
[57]
Imai, K. Allosteric effects in haemoglobin; Cambridge University Press, 1982.
[58]
Edelstein, S.J.; Edsall, J.T. Linkage between ligand binding and the dimer-tetramer equilibrium in the Monod-Wyman-Changeux model of hemoglobin. Proc. Natl. Acad. Sci. USA, 1986, 83(11), 3796-3800.
[http://dx.doi.org/10.1073/pnas.83.11.3796] [PMID: 3459157]
[59]
Ackers, G.K. Deciphering the molecular code of hemoglobin allostery. Adv. Protein Chem., 1998, 51, 185-253.
[http://dx.doi.org/10.1016/S0065-3233(08)60653-1] [PMID: 9615171]
[60]
Ackers, G.K.; Holt, J.M. Asymmetric cooperativity in a symmetric tetramer: human hemoglobin. J. Biol. Chem., 2006, 281(17), 11441-11443.
[http://dx.doi.org/10.1074/jbc.R500019200] [PMID: 16423822]

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