Abstract
Interest in protein folding intermediates lies in their significance to protein folding pathways. The molten globule (MG) state is one such intermediate lying on the kinetic (and sometimes thermodynamic) pathway between native and unfolded states. Development of our qualitative and quantitative understanding of the MG state can provide deeper insight into the folding pathways and hence potentially facilitate solution of the protein folding problem. An extensive look at literature suggests that most studies into protein MG states have been largely qualitative. Attempts to obtain quantitative insights into MG states have involved application of high-sensitivity calorimetry (differential scanning calorimetry and isothermal titration calorimetry). This review addresses the progress made in this direction by discussing the knowledge gained to date, along with the future promise of calorimetry, in providing quantitative information on the structural features of MG states. Particular attention is paid to the question of whether such states share common structural features or not. The difference in the nature of the transition from the MG state to the unfolded state, in terms of cooperativity, has also been addressed and discussed.
Similar content being viewed by others
References
Agashe VR, Shastry MC, Udgaonkar JB (1995) Initial hydrophobic collapse in the folding of barstar. Nature 377:754–757. https://doi.org/10.1038/377754a0
Anfinsen CB, Haber E, Sela M et al (1961) The kinetics of formation of native ribonuclease during oxidation of the reduced polypeptide chain. Proc Natl Acad Sci U S A 47:1309–1314 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC223141/pdf/pnas00213-0003.pdf
Arai M, Kondrashkina E, Kayatekin C et al (2007) Microsecond hydrophobic collapse in the folding of Escherichia coli dihydrofolate reductase, an α/β-type protein. J Mol Biol 368:219–229. https://doi.org/10.1016/j.jmb.2007.01.085
Bai JH, Xu D, Wang HR et al (1999) Evidence for the existence of an unfolding intermediate state for aminoacylase during denaturation in guanidine solutions. Biochim Biophys Acta 1430:39–45. https://doi.org/10.1016/S0167-4838(98)00282-9
Balbach J, Forge V, van Nuland NA et al (1995) Following protein folding in real time using NMR spectroscopy. Nat Struct Biol 2:865–870. https://doi.org/10.1038/nsb1095-865
Baliga C, Selmke B, Worobiew I et al (2019) CcdB at pH 4 forms a partially unfolded state with a dry core. Biophys J 116:807–817. https://doi.org/10.1016/j.bpj.2019.01.026
Banerjee T, Kishore N (2005) 2, 2, 2-Trifluoroethanol-induced molten globule state of concanavalin A and energetics of 8-anilinonaphthalene sulfonate binding: calorimetric and spectroscopic investigation. J Phys Chem B 109:22655–22662. https://doi.org/10.1021/jp053757r
Barrick D, Baldwin RL (1993) The molten globule intermediate of apomyoglobin and the process of protein folding. Protein Sci 2:869–876. https://doi.org/10.1002/pro.5560020601
Bryngelson JD, Onuchic JN, Socci ND et al (1995) Funnels, pathways, and the energy landscape of protein folding: a synthesis. Prot Struct Funct Bioinform 21:167–195. https://doi.org/10.1002/prot.340210302
Bychkova VE, Pain RH, Ptitsyn OB (1988) The ‘molten globule’ state is involved in the translocation of proteins across membranes? FEBS Lett 238:231–234. https://doi.org/10.1016/0014-5793(88)80485-X
Carra JH, Murphy EC, Privalov PL (1996) Thermodynamic effects of mutations on the denaturation of T4 lysozyme. Biophys J 71:1994–2001. https://doi.org/10.1016/S0006-3495(96)79397-9
Chamani J, Moosavi-Movahedi AA, Saboury AA et al (2003) Calorimetric indication of the molten globule-like state of cytochrome c induced by n-alkyl sulfates at low concentrations. J Chem Thermodyn 35:199–207. https://doi.org/10.1016/S0021-9614(02)00312-9
Chiti F, Webster P, Taddei N et al (1999) Designing conditions for in vitro formation of amyloid protofilaments and fibrils. Proc Natl Acad Sci 96:3590–3594. https://doi.org/10.1073/pnas.96.7.3590
Dijkstra MJJ, Fokkink WJ, Heringa J et al (2018) The characteristics of molten globule states and folding pathways strongly depend on the sequence of a protein. Mol Phys 116:3173–3180. https://doi.org/10.1080/00268976.2018.1496290
Dill KA (1985) Theory for the folding and stability of globular proteins. Biochem 24:1501–1509. https://doi.org/10.1021/bi00327a032
Dill KA, MacCallum JL (2012) The protein-folding problem, 50 years on. Science 338:1042–1046. https://doi.org/10.1126/science.1219021
Dill KA, Fiebig KM, Chan HS (1993) Cooperativity in protein-folding kinetics. Proc Natl Acad Sci 90:1942–1946 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC45996/
Dolgikh DA, Abaturov LV, Bolotina IA et al (1985) Compact state of a protein molecule with pronounced small-scale mobility: bovine α-lactalbumin. Eur Biophys J 13:109–121. https://doi.org/10.1007/BF00256531
Ferrer M, Barany G, Woodward C (1995) Partially folded, molten globule and molten coil states of bovine pancreatic trypsin inhibitor. Nat Struct Biol 2:211–217. https://doi.org/10.1038/nsb0395-211
Fersht AR (1997) Nucleation mechanisms in protein folding. Curr Opin Struct Biol 7:3–9. https://doi.org/10.1016/S0959-440X(97)80002-4
Fink AL, Oberg KA, Seshadri S (1998) Discrete intermediates versus molten globule models for protein folding: characterization of partially folded intermediates of apomyoglobin. Fold Des 3:19–25. https://doi.org/10.1016/S1359-0278(98)00005-4
Fisher A, Taniuchi H (1992) A study of core domains, and the core domain-domain interaction of cytochrome c fragment complex. Arch Biochem Biophys 296:1–16. https://doi.org/10.1016/0003-9861(92)90538-8
Forge V, Wijesinha RT, Balbach J et al (1999) Rapid collapse and slow structural reorganisation during the refolding of bovine α-lactalbumin. J Mol Biol 288:673–688. https://doi.org/10.1006/jmbi.1999.2687
Go N (1984) The consistency principle in protein-structure and pathways of folding. Adv Biophys 18:149–164
Goto Y, Calciano LJ, Fink AL (1990) Acid-induced folding of proteins. Proc Natl Acad Sci 87:573–577. https://doi.org/10.1073/pnas.87.2.573
Griko YV, Privalov PL (1994) Thermodynamic puzzle of apomyoglobin unfolding. J Mol Biol 235:1318–1325. https://doi.org/10.1006/jmbi.1994.1085
Gussakovsky EE, Haas E (1995) Two steps in the transition between the native and acid states of bovine α-lactalbumin detected by circular polarization of luminescence: evidence for a premolten globule state? Prot Sci 4:2319–2326. https://doi.org/10.1002/pro.5560041109
Haas E (2005) The study of protein folding and dynamics by determination of intramolecular distance distributions and their fluctuations using ensemble and single-molecule FRET measurements. Chem Phys Chem 6:858–870. https://doi.org/10.1002/cphc.200400617
Haas E (2012) Ensemble FRET methods in studies of intrinsically disordered proteins. In: Uversky V, Dunker A (eds) Intrinsically disordered protein analysis. Methods in molecular biology (methods and protocols), vol 895. Humana Press, Totowa, NJ
Haber E, Anfinsen CB (1962) Side-chain interactions governing the pairing of half-cystine residues in ribonuclease. J Biol Chem 237:1839–1844
Hamada D, Kidokoro S, Fukada H et al (1994) Salt-induced formation of the molten globule state of cytochrome c studied by isothermal titration calorimetry. Proc Natl Acad Sci 91:10325–10329. https://doi.org/10.1073/pnas.91.22.10325
Hamada D, Fukada H, Takahashi K et al (1995) Salt-induced formation of the molten globule state of apomyoglobin studied by isothermal titration calorimetry. Thermochim Acta 266:385–400. https://doi.org/10.1016/0040-6031(95)02444-1
Hammarströ P, Persson M, Freskgård P-O, Mårtensson L-G, Andersson D, Jonsson B-H, Carlsson U (1999) Structural mapping of an aggregation nucleation site in a molten globule intermediate. J Biol Chem 27:32897–32903. https://doi.org/10.1074/jbc.274.46.32897
Hawe A, Sutter M, Jiskoot W (2008) Extrinsic fluorescent dyes as tools for protein characterization. Pharm Res 25:1487–1499. https://doi.org/10.1007/s11095-007-9516-9
Haynie DT, Freire E (1993) Structural energetics of the molten globule state. Prot Struct Funct Bioinform 16:115–140. https://doi.org/10.1002/prot.340160202
Honda RP, Yamaguchi KI, Kuwata K (2014) Acid-induced molten globule state of a prion protein crucial role of strand 1-helix 1-strand 2 segment. J Biol Chem 289:30355–30363. https://doi.org/10.1074/jbc.M114.559450
Iglesias MM, Elola MT, Martinez V et al (2003) Identification of an equilibrium intermediate in the unfolding process of galectin-1, which retains its carbohydrate-binding specificity. Biochim Biophys Acta Proteins Proteomics 1648:164–173. https://doi.org/10.1016/S1570-9639(03)00119-5
Ithychanda SS, Dou K, Robertson SP et al (2017) Structural and thermodynamic basis of a frontometaphyseal dysplasia mutation in filamin A. J Biol Chem 292:8390–8400. https://doi.org/10.1074/jbc.M117.776740
Jain R, Sharma D, Kumar R et al (2018) Structural, kinetic and thermodynamic characterizations of SDS-induced molten globule state of a highly negatively charged cytochrome c. J Biochem 165:125–137. https://doi.org/10.1093/jb/mvy087
Jeng MF, Englander SW (1991) Stable submolecular folding units in a non-compact form of cytochrome c. J Mol Biol 221:1045–1061. https://doi.org/10.1016/0022-2836(91)80191-V
Jennings PA, Wright PE (1993) Formation of a molten globule intermediate early in the kinetic folding pathway of apomyoglobin. Sci 262:892–896. https://doi.org/10.1126/science.8235610
Karplus M, Weaver DL (1976) Protein-folding dynamics. Nature 260:404–406. https://doi.org/10.1038/260404a0
Kelly JW (1998) The alternative conformations of amyloidogenic proteins and their multi-step assembly pathways. Curr Opin Struct Biol 8:101–106. https://doi.org/10.1016/S0959-440X(98)80016-X
Khan MKA, Rahaman H, Ahmad F (2011) Conformation and thermodynamic stability of pre-molten and molten globule states of mammalian cytochromes-c. Metallomics 3(4):327–338. https://doi.org/10.1039/C0MT00078G
Kim PS, Baldwin RL (1982) Specific intermediates in the folding reactions of small proteins and the mechanism of protein folding. Annu Rev Biochem 51:459–489. https://doi.org/10.1146/annurev.bi.51.070182.002331
Koshiba T, Yao M, Kobashigawa Y et al (2000) Structure and thermodynamics of the extraordinarily stable molten globule state of canine milk lysozyme. Biochem 39:3248–3257. https://doi.org/10.1021/bi991525a
Koshiba T, Kobashigawa Y, Demura M et al (2001) Energetics of three-state unfolding of a protein: canine milk lysozyme. Protein Eng 14:967–974. https://doi.org/10.1093/protein/14.12.967
Kozak JJ, Gray HB, Wittung-Stafshede P (2018) Geometrical description of protein structural motifs. J Phys Chem B 122:11289–11294. https://doi.org/10.1021/acs.jpcb.8b07130
Kulkarni P, Uversky VN (2018) Intrinsically disordered proteins and the Janus challenge. Biomol 8:179. https://doi.org/10.3390/biom8040179
Kuroda Y, Kidokoro SI, Wada A (1992) Thermodynamic characterization of cytochrome c at low pH: observation of the molten globule state and of the cold denaturation process. J Mol Biol 223:1139–1153. https://doi.org/10.1016/0022-2836(92)90265-L
Kuwajima K (1989) The molten globule state as a clue for understanding the folding and cooperativity of globular protein structure. Prot Struct Funct Bioinformatics 6:87–103. https://doi.org/10.1002/prot.340060202
Ladbury JE, Doyle ML (eds) (2004) Biocalorimetry 2: applications of calorimetry in the biological sciences. John Wiley & Sons
Martin J, Langer T, Boteva R et al (1991) Chaperonin-mediated protein folding at the surface of groEL through a ‘molten globule’-like intermediate. Nat 352:36–42. https://doi.org/10.1038/352036a0
Mazurenko S, Kunka A, Beerens K et al (2017) Exploration of protein unfolding by modelling calorimetry data from reheating. Sci Rep 7:16321. https://doi.org/10.1038/s41598-017-16360-y
Misra PP, Kishore N (2011) Biophysical analysis of partially folded state of a-lactalbumin in the presence of cationic and anionic surfactants. J Colloid Interface Sci 354:234–247. https://doi.org/10.1016/j.jcis.2010.10.015
Moosavi-Movahedi AA, Chamani J, Gharanfoli M et al (2004) Differential scanning calorimetric study of the molten globule state of cytochrome c induced by sodium n-dodecyl sulfate. Thermochim Acta 409:137–144. https://doi.org/10.1016/S0040-6031(03)00358-7
Munoz V, Thompson PA, Hofrichter J et al (1997) Folding dynamics and mechanism of β-hairpin formation. Nat 390:196–199. https://doi.org/10.1038/36626
Nakamura S, Kidokoro SI (2012) Volumetric properties of the molten globule state of cytochrome c in the thermal three-state transition evaluated by pressure perturbation calorimetry. J Phys Chem B 116:1927–1932. https://doi.org/10.1021/jp209686e
Nakamura S, Baba T, Kidokoro SI (2007) A molten globule-like intermediate state detected in the thermal transition of cytochrome c under low salt concentration. Biophys Chem 127:103–112. https://doi.org/10.1016/j.bpc.2007.01.002
Nakamura S, Seki Y, Katoh E et al (2011) Thermodynamic and structural properties of the acid molten globule state of horse cytochrome c. Biochem 50:3116–3126. https://doi.org/10.1021/bi101806b
Nishii I, Kataoka M, Goto Y (1995) Thermodynamic stability of the molten globule states of apomyoglobin. J Mol Biol 250:223–238. https://doi.org/10.1006/jmbi.1995.0373
Nölting B, Agard DA (2008) How general is the nucleation–condensation mechanism? Prot Struct Funct Bioinform 73:754–764. https://doi.org/10.1002/prot.22099
Ohgushi M, Wada A (1983) Molten-globule state: a compact form of globular proteins with mobile side-chains. FEBS Lett 28:21–24. https://doi.org/10.1016/0014-5793(83)80010-6
Onuchic JN, Socci ND, Luthey-Schulten Z et al (1996) Protein folding funnels: the nature of the transition state ensemble. Fold Des 1:441–450. https://doi.org/10.1016/S1359-0278(96)00060-0
Onuchic JN, Luthey-Schulten Z, Wolynes PG (1997) Theory of protein folding: the energy landscape perspective. Annu Rev Phys Chem 48:545–600. https://doi.org/10.1146/annurev.physchem.48.1.545
Paci E, Smith LJ, Dobson CM et al (2001) Exploration of partially unfolded states of human α-lactalbumin by molecular dynamics simulation. J Mol Biol 306:329–347. https://doi.org/10.1006/jmbi.2000.4337
Peixoto PD, Trivelli X, André C et al (2019) Formation of β-lactoglobulin aggregates from quite, unfolded conformations upon heat activation. Langmuir 35:446–452. https://doi.org/10.1021/acs.langmuir.8b03459
Penkett CJ, Redfield C, Jones JA et al (1998) Structural and dynamical characterization of a biologically active unfolded fibronectin-binding protein from Staphylococcus a ureus. Biochem 37:17054–17067. https://doi.org/10.1021/bi9814080
Perutz MF, Rossman MG, Cullis AF et al (1960) Structure of haemoglobin: a three-dimensional Fourier synthesis at 5.5-Ao. resolution, obtained by X-ray analysis. Nature 185:416–422 https://www.ncbi.nlm.nih.gov/pubmed/18990801
Potekhin S, Pfeil W (1989) Microcalorimetric studies of conformational transitions of ferricytochrome c in acidic solution. Biophys Chem 34:55–62. https://doi.org/10.1016/0301-4622(89)80041-9
Povarova OI, Kuznetsova IM, Turoverov KK (2010) Differences in the pathways of proteins unfolding induced by urea and guanidine hydrochloride: molten globule state and aggregates. PLoS One 132:e15035. https://doi.org/10.1371/journal.pone.0015035
Prajapati RS, Indu S, Varadarajan R (2007) Identification and thermodynamic characterization of molten globule states of periplasmic binding proteins. Biochem 46:10339–10352. https://doi.org/10.1021/bi700577m
Privalov PL (1979) Stability of proteins: small globular proteins. Adv Prot Chem 33:167–241). Academic Press. https://doi.org/10.1016/S0065-3233(08)60460-X
Privalov PL, Dragan AI (2007) Microcalorimetry of biological macromolecules. Biophys Chem 126:16–24. https://doi.org/10.1016/j.bpc.2006.05.004
Privalov PL, Gill SJ (1988). Stability of protein structure and hydrophobic interaction. Adv Prot Chem 39:191–234. Academic Press. https://doi.org/10.1016/S0065-3233(08)60377-0
Ptitsyn OB (1973) Stages in the mechanism of self-organization of protein molecules. Dol Akad Nauk, SSSR 210:1213–1215 https://www.ncbi.nlm.nih.gov/pubmed/4721708
Ptitsyn OB (1987) Protein folding: hypotheses and experiments. J Prot Chem 6:273–293. https://doi.org/10.1007/BF00248050
Ptitsyn OB (1995) Molten globule and protein folding. Adv Prot Chem 47:83–229. https://doi.org/10.1016/S0065-3233(08)60546-X
Ptitsyn OB, Rashin AA (1975) A model of myoglobin self-organization. Biophys Chem 3:1–20. https://doi.org/10.1016/0301-4622(75)80033-0
Rackovsky S, Scheraga HA (1977) Hydrophobicity, hydrophilicity, and the radial and orientational distributions of residues in native proteins. Proc Nat Acad Sci 74:5248–5251 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC431666/
Radibratovic M, Al-Hanish A, Minic S (2019) Stabilization of apo α-lactalbumin by binding of epigallocatechin-3-gallate: experimental and molecular dynamics study. Food Chem 278:388–395. https://doi.org/10.1016/j.foodchem.2018.11.038
Rariy RV, Klibanov AM (1997) Correct protein folding in glycerol. Proc Natl Acad Sci U S A 94:13520–13523. https://doi.org/10.1073/pnas.94.25.13520
Redfield C, Smith RA, Dobson CM (1994) Structural characterization of a highly–ordered ‘molten globule’ at low pH. Nat Struct Mol Biol 1:23–29. https://doi.org/10.1038/nsb0194-23
Roder H, Elöve GA, Englander SW (1988) Structural characterization of folding intermediates in cytochrome c by H-exchange labelling and proton NMR. Nature 335:694–699. https://doi.org/10.1038/335700a0
Samaddar S, Mandal AK, Mondal SK et al (2006) Solvation dynamics of a protein in the pre molten globule state. J Phys Chem B 110:21210–21215. https://doi.org/10.1021/jp064136g
Samanta HS, Zhuravlev PI, Hinczewski M et al (2017) Protein collapse is encoded in the folded state architecture. Soft Matt 13:3622–3638. https://doi.org/10.1039/C7SM00074J
Sasahara K, Demura M, Nitta K (2000) Partially unfolded equilibrium state of hen lysozyme studied by circular dichroism spectroscopy. Biochemistry 39:6475–6482. https://doi.org/10.1021/bi992560k
Sato S, Ward CL, Krouse ME et al (1996) Glycerol reverses the misfolding phenotype of the most common cystic fibrosis mutation. J Biol Chem 271:635–638. https://doi.org/10.1074/jbc.271.2.635
Schweiker KL, Fitz VW, Makhatadze GI (2009) Universal convergence of the specific volume changes of globular proteins upon unfolding. Biochem 48:10846–10851. https://doi.org/10.1021/bi901220u
Semisotnov GV, Rodionova NA, Razgulyaev OI et al (1991) Study of the “molten globule” intermediate state in protein folding by a hydrophobic fluorescent probe. Biopoly Orig Res Biomol 31:119–128. https://doi.org/10.1002/bip.360310111
Shakhnovich EI, Finkelstein AV (1989) Theory of cooperative transitions in protein molecules. I. Why denaturation of globular protein is a first order phase transition. Biopoly Orig Res Biomol 28:1667–1680. https://doi.org/10.1002/bip.360281003
Sharma R, Kishore N (2008) Isothermal titration calorimetric and spectroscopic studies on (alcohol+ salt) induced partially folded state of α-lactalbumin and its binding with 8-anilino-1-naphthalenesulfonic acid. J Chem Thermo 40:1141–1151. https://doi.org/10.1016/j.jct.2008.02.009
Sheshadri S, Lingaraju GM, Varadarajan R (1999) Denaturant mediated unfolding of both native and molten globule states of maltose binding protein are accompanied by large ΔCp’s. Protein Sci 8:1689–1695. https://doi.org/10.1110/ps.8.8.1689
Singh SK, Kishore N (2006) Elucidating the binding thermodynamics of 8-anilino-1-naphthalene sulfonic acid with the A-state of α-lactalbumin: an isothermal titration calorimetric investigation. Biopoly Orig Res Biomol 83:205–212. https://doi.org/10.1002/bip.20547
Skora L, Becker S, Zweckstetter M (2010) Molten globule precursor states are conformationally correlated to amyloid fibrils of human beta-2-microglobulin. J Am Chem Soc 132:9223–9225. https://doi.org/10.1021/ja100453e
Stryer L (1965) The interaction of a naphthalene dye with apomyoglobin and apohemoglobin: a fluorescent probe of non-polar binding sites. J Mol Biol 13:482–495. https://doi.org/10.1016/S0022-2836(65)80111-5
Svensson M, Sabharwal H, Håkansson A et al (1999) Molecular characterization of α–lactalbumin folding variants that induce apoptosis in tumor cells. J Biol Chem 274:6388–6396. https://doi.org/10.1074/jbc.274.10.6388
Swaminathan R, Periasamy N, Udgaonkar JB et al (1994) Molten globule-like conformation of barstar: a study by fluorescence dynamics. J Phys Chem 98:9270–9278. https://doi.org/10.1021/j100088a030
Takahashi S, Yoshida A, Oikawa H (2018) Hypothesis: structural heterogeneity of the unfolded proteins originating from the coupling of the local clusters and the long-range distance distribution. Biophys Rev 10:363–373. https://doi.org/10.1007/s12551-018-0405-8
Talele P, Kishore N (2015) Thermodynamic analysis of partially folded states of myoglobin in presence of 2, 2, 2-trifluoroethanol. J Chem Thermo 84:50–59. https://doi.org/10.1016/j.jct.2014.12.019
Tyagi M, Bornot A, Offmann B, de Brevern AG (2009) Analysis of loop boundaries using different local structure assignment methods. Protein Sci 18:1869–1881. https://doi.org/10.1002/pro.198
Udgaonkar JB, Baldwin RL (1988) NMR evidence for an early framework intermediate on the folding pathway of ribonuclease A. Nature 335 (6192):694-699
Uversky VN (2018) Bringing darkness to light: intrinsic disorder as a means to dig into the dark proteome. Proteomics 18:1800352. https://doi.org/10.1002/pmic.201800352
Uversky VN, Karnoup AS, Segel DJ et al (1998) Anion-induced folding of staphylococcal nuclease: characterization of multiple equilibrium partially folded intermediates. J Mol Biol 278:879–894. https://doi.org/10.1006/jmbi.1998.1741
Van der Goot FG, Gonzalez-Manas JM, Lakey JH et al (1991) A molten-globule membrane-insertion intermediate of the pore-forming domain of colicin A. Nat 354:408–410. https://doi.org/10.1038/354408a0
Vassilenko KS, Uversky VN (2002) Native-like secondary structure of molten globules. Biochim Biophys Acta Prot Struct Mol Enzy 1594:168–177. https://doi.org/10.1016/S0167-4838(01)00303-X
Velicelebi G, Sturtevant JM (1979) Thermodynamics of the denaturation of lysozyme in alcohol-water mixtures. Biochem 18:1180–1186. https://doi.org/10.1021/bi00574a010
Wirtz H, Schafer S, Hoberg C et al (2018) Hydrophobic collapse of ubiquitin generates rapid protein–water motions. Biochem 57:3650–3657. https://doi.org/10.1021/acs.biochem.8b00235
Wolynes PG, Onuchic JN, Thirumalai D (1995) Navigating the folding routes. Sci 267:1619–1619. https://doi.org/10.1126/science.7886447
Xie D, Bhakuni V, Freire E (1991) Calorimetric determination of the energetics of the molten globule intermediate in protein folding: apo-.alpha.-lactalbumin. Biochem 30:10673–10678. https://doi.org/10.1021/bi00108a010
Xie D, Bhakuni V, Freire E (1993) Are the molten globule and the unfolded states of apo-α-lactalbumin enthalpically equivalent? J Mol Biol 232:5–8. https://doi.org/10.1006/jmbi.1993.1364
Xie Q, Guo T, Wang T et al (2003) Aspartate-induced aminoacylase folding and forming of molten globule. Int J Biochem Cell Biol 35:1558–1572. https://doi.org/10.1016/S1357-2725(03)00131-6
Yutani K, Ogasahara K, Kuwajima K (1992) Absence of the thermal transition in apo-α-lactalbumin in the molten globule state: a study by differential scanning microcalorimetry. J Mol Biol 228:347–350. https://doi.org/10.1016/0022-2836(92)90824-4
Zhang JS, Yang LQ, Du BR et al (2017) Higher RABEX-5 mRNA predicts unfavourable survival in patients with colorectal cancer. Eur Rev Med Pharma Sci 21:2372–2376 https://www.europeanreview.org/article/12807
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Judy, E., Kishore, N. A look back at the molten globule state of proteins: thermodynamic aspects. Biophys Rev 11, 365–375 (2019). https://doi.org/10.1007/s12551-019-00527-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12551-019-00527-0