Contribution of Disulfide Bonds to Stability, Folding, and Amyloid Fibril Formation: The PI3-SH3 Domain Case

Graña-Montes, Ricardo; Groot, Natalia Sánchez de; Castillo, Virginia Leyva; Sancho, Javier; Velázquez‐Campoy, Adrián; Ventura, Salvador

doi:10.1089/ars.2011.3936

Cited by 32 publications

(25 citation statements)

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“…Pairs of cysteines can oxidize to form disulfide bonds, which contribute to the correct fold and functionality of proteins (40). Importantly, inter-or intramolecular disulfide bonding has been shown to promote or at least stabilize amyloid fibers (41,42). Furthermore, reducing environments can inhibit or delay amyloidogenesis by blocking intermolecular bonding and thereby preventing fiber growth (34,43).…”

Section: Discussionmentioning

confidence: 99%

Functional Analysis of the Accessory Protein TapA in Bacillus subtilis Amyloid Fiber Assembly

et al. 2014

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bBacillus subtilis biofilm formation relies on the assembly of a fibrous scaffold formed by the protein TasA. TasA polymerizes into highly stable fibers with biochemical and morphological features of functional amyloids. Previously, we showed that assembly of TasA fibers requires the auxiliary protein TapA. In this study, we investigated the roles of TapA sequences from the C-terminal and N-terminal ends and TapA cysteine residues in its ability to promote the assembly of TasA amyloid-like fibers. We found that the cysteine residues are not essential for the formation of TasA fibers, as their replacement by alanine residues resulted in only minor defects in biofilm formation. Mutating sequences in the C-terminal half had no effect on biofilm formation. However, we identified a sequence of 8 amino acids in the N terminus that is key for TasA fiber formation. Strains expressing TapA lacking these 8 residues were completely defective in biofilm formation. In addition, this TapA mutant protein exhibited a dominant negative effect on TasA fiber formation. Even in the presence of wild-type TapA, the mutant protein inhibited fiber assembly in vitro and delayed biofilm formation in vivo. We propose that this 8-residue sequence is crucial for the formation of amyloid-like fibers on the cell surface, perhaps by mediating the interaction between TapA or TapA and TasA molecules.

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Section: Discussionmentioning

confidence: 99%

Functional Analysis of the Accessory Protein TapA in Bacillus subtilis Amyloid Fiber Assembly

et al. 2014

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“…In globular proteins, disulfide bonds strongly stabilize the structure, thus minimizing unfolding reactions that might expose previously hidden APRs (43). This is likely the underlying reason explaining why, as a trend, globular proteins with disulfides bonds tend to display more aggregation-prone sequences than proteins devoid of this bond (63).…”

Section: Respectively) (E)mentioning

confidence: 99%

Association Between Foldability and Aggregation Propensity in Small Disulfide-Rich Proteins

Fraga

Graña-Montes²,

Illa³

et al. 2014

Antioxidants & Redox Signaling

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Aims: Disulfide-rich domains (DRDs) are small proteins whose native structure is stabilized by the presence of covalent disulfide bonds. These domains are versatile and can perform a wide range of functions. Many of these domains readily unfold on disulfide bond reduction, suggesting that in the absence of covalent bonding they might display significant disorder. Results: Here, we analyzed the degree of disorder in 97 domains representative of the different DRDs families and demonstrate that, in terms of sequence, many of them can be classified as intrinsically disordered proteins (IDPs) or contain predicted disordered regions. The analysis of the aggregation propensity of these domains indicates that, similar to IDPs, their sequences are more soluble and have less aggregating regions than those of other globular domains, suggesting that they might have evolved to avoid aggregation after protein synthesis and before they can attain its compact and covalently linked native structure. Innovation and Conclusion: DRDs, which resemble IDPs in the reduced state and become globular when their disulfide bonds are formed, illustrate the link between protein folding and aggregation propensities and how these two properties cannot be easily dissociated, determining the main traits of the folding routes followed by these small proteins to attain their native oxidized states. Antioxid. Redox Signal. 21, 368-383.

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“…Hence, the presence of these groups has substantial impact on the aggregation and gelation behavior of a wide variety of proteins which has been confirmed by many researchers (Arntfield et al, 1991;Broersen et al, 2006;Graña-Montes et al, 2011;Hayakawa & Nakai, 1985;Hoffmann & van Mil, 1997;Margoshes, 1990;Mine, 1992;Sawyer, 1968;Shimada & Cheftel, 1989). A variety of modifications can be performed targeting sulfhydryl groups, which are part of the cysteine residues.…”

Section: Chemical-reactive Groupsmentioning

confidence: 92%

Application Potential of Food Protein Modification

Jongh¹,

Broersen²

2012

Advances in Chemical Engineering

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Contribution of Disulfide Bonds to Stability, Folding, and Amyloid Fibril Formation: The PI3-SH3 Domain Case

Abstract: Disulfide bridges may act as key molecular determinants of both productive protein folding and deleterious aggregation reactions.

Cited by 32 publications

References 50 publications

Functional Analysis of the Accessory Protein TapA in Bacillus subtilis Amyloid Fiber Assembly

Functional Analysis of the Accessory Protein TapA in Bacillus subtilis Amyloid Fiber Assembly

Association Between Foldability and Aggregation Propensity in Small Disulfide-Rich Proteins

Application Potential of Food Protein Modification

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