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Plasticity within the obligatory folding nucleus of an immunoglobulin-like domain.

Lappalainen I, Hurley MG, Clarke J - J. Mol. Biol. (2007)

Bottom Line: However, there are rare examples where this nucleation pattern is absent.In this study, we have investigated the folding of a novel member of the fnIII superfamily whose nucleus appears to lack one of the four buried hydrophobic residues.We show that the folding mechanism is unaltered, but the folding nucleus has moved within the hydrophobic core.

View Article: PubMed Central - PubMed

Affiliation: University of Cambridge Department of Chemistry, MRC Centre for Protein Engineering, Lensfield Rd, Cambridge CB2 1EW, UK.

ABSTRACT
A number of beta-sandwich immunoglobulin-like domains have been shown to fold using a set of structurally equivalent residues that form a folding nucleus deep within the core of the protein. Formation of this nucleus is sufficient to establish the complex Greek key topology of the native state. These nucleating residues are highly conserved within the immunoglobulin superfamily, but are less well conserved in the fibronectin type III (fnIII) superfamily, where the requirement is simply to have four interacting hydrophobic residues. However, there are rare examples where this nucleation pattern is absent. In this study, we have investigated the folding of a novel member of the fnIII superfamily whose nucleus appears to lack one of the four buried hydrophobic residues. We show that the folding mechanism is unaltered, but the folding nucleus has moved within the hydrophobic core.

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Related in: MedlinePlus

Brønsted analysis of TNfn3 and CAfn2 mutants, showing the plot ofΔΔGD–‡versus ΔΔGD–N.The separation of data points into two discrete populations shows that thefolding nucleus of both proteins is not a uniformly expanded form of the nativestate. The central core of the protein forms early and the peripheral regionspack after the transition state for folding.
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fig7: Brønsted analysis of TNfn3 and CAfn2 mutants, showing the plot ofΔΔGD–‡versus ΔΔGD–N.The separation of data points into two discrete populations shows that thefolding nucleus of both proteins is not a uniformly expanded form of the nativestate. The central core of the protein forms early and the peripheral regionspack after the transition state for folding.

Mentions: The Φ-values for TNfn3 are generally higher than those in CAfn2,ranging from 0 to 0.6;18 however, the pattern of Φ-values is similar. For bothproteins, the mutational results can be separated into two classes. Thefirst group consists of residues in the central β-strands, which showsignificant formation of structure in the transition state. The second groupconsists of mutations probing the terminal A and G-strands, and residuesfrom the extremities of the central strands. These two populations areclearly observed in a Brønsted plot (Figure7).


Plasticity within the obligatory folding nucleus of an immunoglobulin-like domain.

Lappalainen I, Hurley MG, Clarke J - J. Mol. Biol. (2007)

Brønsted analysis of TNfn3 and CAfn2 mutants, showing the plot ofΔΔGD–‡versus ΔΔGD–N.The separation of data points into two discrete populations shows that thefolding nucleus of both proteins is not a uniformly expanded form of the nativestate. The central core of the protein forms early and the peripheral regionspack after the transition state for folding.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2291451&req=5

fig7: Brønsted analysis of TNfn3 and CAfn2 mutants, showing the plot ofΔΔGD–‡versus ΔΔGD–N.The separation of data points into two discrete populations shows that thefolding nucleus of both proteins is not a uniformly expanded form of the nativestate. The central core of the protein forms early and the peripheral regionspack after the transition state for folding.
Mentions: The Φ-values for TNfn3 are generally higher than those in CAfn2,ranging from 0 to 0.6;18 however, the pattern of Φ-values is similar. For bothproteins, the mutational results can be separated into two classes. Thefirst group consists of residues in the central β-strands, which showsignificant formation of structure in the transition state. The second groupconsists of mutations probing the terminal A and G-strands, and residuesfrom the extremities of the central strands. These two populations areclearly observed in a Brønsted plot (Figure7).

Bottom Line: However, there are rare examples where this nucleation pattern is absent.In this study, we have investigated the folding of a novel member of the fnIII superfamily whose nucleus appears to lack one of the four buried hydrophobic residues.We show that the folding mechanism is unaltered, but the folding nucleus has moved within the hydrophobic core.

View Article: PubMed Central - PubMed

Affiliation: University of Cambridge Department of Chemistry, MRC Centre for Protein Engineering, Lensfield Rd, Cambridge CB2 1EW, UK.

ABSTRACT
A number of beta-sandwich immunoglobulin-like domains have been shown to fold using a set of structurally equivalent residues that form a folding nucleus deep within the core of the protein. Formation of this nucleus is sufficient to establish the complex Greek key topology of the native state. These nucleating residues are highly conserved within the immunoglobulin superfamily, but are less well conserved in the fibronectin type III (fnIII) superfamily, where the requirement is simply to have four interacting hydrophobic residues. However, there are rare examples where this nucleation pattern is absent. In this study, we have investigated the folding of a novel member of the fnIII superfamily whose nucleus appears to lack one of the four buried hydrophobic residues. We show that the folding mechanism is unaltered, but the folding nucleus has moved within the hydrophobic core.

Show MeSH
Related in: MedlinePlus