The “Pre-Molten Globule,” a New Intermediate in Protein Folding

Chaffotte, Alain; Guijarro, J. Iñaki; Guillou, Yvonne; Delepierre, Muriel; Goldberg, Michel

doi:10.1023/a:1026397008011

Cited by 36 publications

(21 citation statements)

References 23 publications

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“…Measurements of the secondary structure of the monomer by circular dichroism (CD) similarly indicate a small amount of secondary structure. Specifically, the NMR, CD, and diffusion measurements indicate monomeric hIAPP adopts a state similar to the premolten globule state in protein folding, with fluctuating metastable structure and condensed fold that is less compact than an unfolded protein but lacking the well-packed core of a natively folded protein [ 27 ]. This state appears to be particularly aggregation-prone in general; many other amyloidogenic peptides and proteins also appear to be premolten globules of this type [ 28 – 30 ].…”

Section: The Iapp Aggregation Pathwaymentioning

confidence: 99%

Inhibition of IAPP Aggregation and Toxicity by Natural Products and Derivatives

Pithadia

Brender

Fierke

et al. 2016

Journal of Diabetes Research

117

111

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Fibrillar aggregates of human islet amyloid polypeptide, hIAPP, a pathological feature seen in some diabetes patients, are a likely causative agent for pancreatic beta-cell toxicity, leading to a transition from a state of insulin resistance to type II diabetes through the loss of insulin producing beta-cells by hIAPP induced toxicity. Because of the probable link between hIAPP and the development of type II diabetes, there has been strong interest in developing reagents to study the aggregation of hIAPP and possible therapeutics to block its toxic effects. Natural products are a class of compounds with interesting pharmacological properties against amyloids which have made them interesting targets to study hIAPP. Specifically, the ability of polyphenolic natural products, EGCG, curcumin, and resveratrol, to modulate the aggregation of hIAPP is discussed. Furthermore, we have outlined possible mechanistic discoveries of the interaction of these small molecules with the peptide and how they may mitigate toxicity associated with peptide aggregation. These abundantly found agents have been long used to combat diseases for many years and may serve as useful templates toward developing therapeutics against hIAPP aggregation and toxicity.

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Section: The Iapp Aggregation Pathwaymentioning

confidence: 99%

Inhibition of IAPP Aggregation and Toxicity by Natural Products and Derivatives

Pithadia

Brender

Fierke

et al. 2016

Journal of Diabetes Research

117

111

View full text Add to dashboard Cite

show abstract

“…39,47 Kinetic experiments on folding of proteins have revealed the presence of an intermediate having less structure than MG states. 57,58 This state was called the pre-molten globule state. The term ''pre-molten globule'' was first proposed by Jeng and Englander.…”

Section: Introductionmentioning

confidence: 99%

Conformation and thermodynamic stability of pre-molten and molten globule states of mammalian cytochromes-c

2011

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Proteins in cells fold via a number of intermediates. These intermediates are quite important as they guide the protein to attain its unique native conformation. To solve the immensely difficult problem of protein folding, it is necessary to characterize intermediates which will unravel the mystery of the steps involved in the proper folding of proteins. Cytochromes-c (cyts-c) have played an important role in studies of the earliest events and intermediates in protein folding. They have always been considered as model proteins for protein folding studies due to their intrinsic properties that can be measured by multiple probes. A large number of different solvent conditions have been employed to obtain equilibrium intermediates of cyts-c. These intermediates show structural heterogeneity which is mainly due to the different solvent conditions used to induce them. In this review we present results of conformational and thermodynamic characterization of equilibrium intermediates (molten globules and pre-molten globules) of the mammalian cyts-c under different solvent conditions.

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“…The second state, a pre-molten globule like state, has [θ] 200 = −10,700±1300° cm 2 dmol −1 and [θ] 222 = −3900± 1100° cm 2 dmol −1 . The pre-molten globule state was first defined in 1997 as a short-lived intermediate in the folding pathway of the trypto-phan synthase beta subunit [54]. One of the key structural differences between these two states is the polyproline II (P II ) helix content.…”

Section: Resultsmentioning

confidence: 99%

FlgM proteins from different bacteria exhibit different structural characteristics

Kit

Hendrix

Stewart

et al. 2013

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

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Intrinsically disordered proteins (IDPs) are a unique class of proteins that do not require a stable structure for function. The importance of IDPs in many biological processes has been established but there remain unanswered questions about their evolution and conservation of their disordered state within a protein family. Our group has been studying the structural similarities among orthologous FlgM proteins, a model class of IDPs. We have previously shown that the FlgM protein from the thermophile Aquifex aeolicus has more structure at A. aeolicus' physiological temperature (85 °C) than is observed for the Salmonella typhimurium FlgM, suggesting that the disordered nature of FlgM varies among organisms and is not universally conserved. In this work, we extend these studies to the FlgM proteins from Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, and Bacillus subtilis. We demonstrate that the B. subtilis, E. coli, and S. typhimurium FlgMs exist in a premolten globule-like conformation, though the B. subtilis FlgM is in a more compacted conformation than the other two. The P. aeruginosa and P. mirabilis FlgM proteins exist in a currently unknown conformation that is not either coil-like or premolten globule-like. The P. aeruginosa FlgM appears to contain more weak intramolecular contacts given its more compacted state than the P. mirabilis FlgM. These results provide experimental evidence that members of the same protein family can exhibit different degrees of disorder, though understanding how different disordered states evolve in the same protein family will require more study.

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The “Pre-Molten Globule,” a New Intermediate in Protein Folding

Cited by 36 publications

References 23 publications

Inhibition of IAPP Aggregation and Toxicity by Natural Products and Derivatives

Inhibition of IAPP Aggregation and Toxicity by Natural Products and Derivatives

Conformation and thermodynamic stability of pre-molten and molten globule states of mammalian cytochromes-c

FlgM proteins from different bacteria exhibit different structural characteristics

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