55:
native-like topology in 8M urea, while nonnative lysozyme contains hydrophobic clusters held together by long-range interactions. By rapidly adjusting experimental conditions to favor native structure formation, relatively compact protein folding intermediates have been observed. These kinetic intermediates - coined molten globules - exhibit native-like secondary structure and fluctuating tertiary structure.
51:
hydrophobic collapse model - the formation of a loosely packed tertiary structure precedes secondary structure acquisition. A nucleation-condensation mechanism involving concomitant formation of short and long-range interactions combines features of both extreme models and thereby represents a unifying mechanism of protein folding.
50:
Protein folding is navigated by a dynamic interplay of secondary and tertiary interactions. Two extreme folding pathway models have been formulated. In the first - the framework model - rapidly formed secondary structure elements assemble into a native tertiary structure. In the second - the
54:
During folding, proteins span a continuum of conformers starting from the denature and ending at the native state. Although often considered a statistical random coil, the denatured state can retain residual structure that mediates (re)folding. For instance, staphylococcal nuclease retains
255:
is achieving the side chain packing needed to create a stable native state rather than an ensemble of molten globules. Given a desired backbone conformation, side chain packing can be designed using variations of the
628:
Jaremko, M., Jaremko, L., Kim, H.-Y., Cho, M.-K., Schwieters, C. D., Giller, K., Becker, S., Zweckstetter, M. (2013) Cold denaturation of a protein dimer monitored at atomic resolution, Nat. Chem. Biol. 9, 264-270
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Klein-Seetharaman, J.; Oikawa, M.; Grimshaw, S. B.; Wirmer, J.; Duchard, E.; Ueda, T.; Imoto, T.; Smith, L. J.; Dobson, C. M.; Schwalbe, H. (2002). "Long-range interactions within a nonnative protein".
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The term "molten globule" may be used to describe various types of partially-folded protein states found in slightly denaturing conditions such as low pH (generally pH = 2), mild denaturant, or high
241:
113:
higher in energy than the native state but lower than the denatured state. The molten globule ensembles sampled during protein folding and unfolding are thought to be roughly similar.
193:
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Kuroda Y, Kidokoro S, Wada A (1992). "Thermodynamic characterization of cytochrome c at low pH. Observation of the molten globule state and of the cold denaturation process".
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101:, respectively. These traits are similar to those observed in the transient intermediate states found during the folding of certain proteins, especially
93:. Molten globules are collapsed and generally have some native-like secondary structure but a dynamic tertiary structure as seen by far-UV and near-UV
109:, and therefore the term "molten globule" is also used to refer to certain protein folding intermediates corresponding to the narrowing region of the
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algorithm; however, attempts to design proteins of novel folds have difficulty using this method due to an absence of plausible backbone models.
424:
Cecconi, C.; Shank, E. A.; Bustamante, C.; Marqusee, S. (2005). "Direct observation of the three-state folding of a single protein molecule".
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The molten globule state can also be thermodynamically accessed under mildly denaturing conditions. It was found, for example, in
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and no apparent "switch" from one form to the other. The folding of some proteins can be modeled as a three-state
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Shortle, D.; Ackerman, M. S. (2001). "Persistence of native-like topology in a denatured protein in 8M urea".
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states that are more or less compact (hence the "globule"), but are lacking the specific tight packing of
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Baldwin RL; Rose GD (2013). "Molten globules, entropy-driven conformational change and protein folding".
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86:, demonstrating for the first time the existence of a third equilibrium (i.e., intermediate) state.
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74:. For cytochrome c and some other proteins, it has been shown that the molten globule state is a "
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Kim, P. S.; Baldwin, R. L. (1990). "Intermediates in the folding reactions of small proteins".
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Bieri O, Kiefhaber T (2000-12-15). "Kinetic models in protein folding". In RH Pain (ed.).
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Daggett, V.; Fersht, A. R. (2003). "Is there a unifying mechanism for protein folding?".
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494:"'Molten-globule state': a compact form of globular proteins with mobile side-chains"
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Dill, K. A. (1985). "Theory for the folding and stability of globular proteins".
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The MG structure is believed to lack the close packing of amino acid
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content but without the tightly packed protein interior, under low
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Ptitsyn, O. (1995). "Molten globule and protein folding".
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Dill, K. A.; Shortle, D. "Denatured states of proteins".
164:) state to a molten globule may be a two state process
568:(2nd ed.). Oxford, UK: Oxford University Press.
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of completely folded proteins (hence the "molten").
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236:{\displaystyle {\ce {U <-> MG <-> N}}}
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188:{\displaystyle {\ce {U <-> MG}}}
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120:that characterize the native state (
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270:Intrinsically disordered proteins
62:, which conserves a native-like
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16:Partially-folded protein state
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583:Pande VS, Rokhsar DS (1998).
566:Mechanisms in Protein Folding
549:10.1016/0022-2836(92)90265-l
511:10.1016/0014-5793(83)80010-6
246:One of the difficulties in
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492:Ohgushi M, Wada A (1983).
472:10.1016/j.sbi.2012.11.004
157:{\displaystyle {\ce {U}}}
135:{\displaystyle {\ce {N}}}
290:Biomolecular condensate
602:10.1073/pnas.95.4.1490
589:Proc Natl Acad Sci USA
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652:Proteins by structure
460:Curr Opin Struct Biol
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285:Hydrophobic collapse
258:dead-end elimination
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107:hydrophobic collapse
349:Trends Biochem. Sci
76:thermodynamic state
64:secondary structure
37:amino acid residues
368:Annu. Rev. Biochem
311:Annu. Rev. Biochem
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95:circular dichroism
72:salt concentration
45:tertiary structure
39:which creates the
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103:globular proteins
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60:cytochrome c
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31:) refers to
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466:(1): 4–10.
428:(262): 892.
118:side chains
91:temperature
41:solid state
23:, the term
647:Proteomics
636:Categories
537:J Mol Biol
296:References
498:FEBS Lett
227:⟷
221:⟷
206:process:
179:⟷
70:and high
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480:23237704
264:See also
82:and the
621:9465042
557:1311387
520:6317443
426:Science
413:: 1719.
407:Science
387:Science
336:: 1501.
249:de novo
204:kinetic
33:protein
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393:: 487.
374:: 795.
317:: 631.
80:native
43:-like
612:19058
524:S2CID
447:: 83.
355:: 18.
97:(CD)
617:PMID
570:ISBN
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516:PMID
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607:PMC
597:doi
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182:MG
68:pH
29:MG
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230:N
218:U
176:U
151:U
129:N
27:(
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