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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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The CAfn2 structure showing the ϕ-values (high, blue, Φ ≥ 0.4; medium, magenta, 0.2 < Φ < 0.4; and low, red, Φ ≤ 0.2). (a) The frontview of CAfn2 (the CAfn2 structure is oriented as in Figure 1). (b) The rear view of CAfn2.
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fig5: The CAfn2 structure showing the ϕ-values (high, blue, Φ ≥ 0.4; medium, magenta, 0.2 < Φ < 0.4; and low, red, Φ ≤ 0.2). (a) The frontview of CAfn2 (the CAfn2 structure is oriented as in Figure 1). (b) The rear view of CAfn2.

Mentions: The CAfn2 Φ-values range from 0 to 0.5, indicating that none of thepositions analyzed is completely structured at the transition state(Table 2). In general, theΦ-values in the A and G-strands are close to 0, while those in the centralB, C, C′, E and F β-strands are higher, and the Φ-values in these centralstrands are higher in the central layers of the core than at the extremes(Figure 3), as observed inTNfn3,18 the tenth fnIII domain of fibronectin (FNfn10)16 and the titin immunoglobulin domain TI I27.17 The Φ-values were classified into low (Φ ≤ 0.2), medium (0.2 < Φ < 0.4) and high (Φ ≥ 0.4)classes. These Φ-values are mapped onto the CAfn2 structure in Figure 5.


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

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

The CAfn2 structure showing the ϕ-values (high, blue, Φ ≥ 0.4; medium, magenta, 0.2 < Φ < 0.4; and low, red, Φ ≤ 0.2). (a) The frontview of CAfn2 (the CAfn2 structure is oriented as in Figure 1). (b) The rear view of CAfn2.
© Copyright Policy
Related In: Results  -  Collection

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

fig5: The CAfn2 structure showing the ϕ-values (high, blue, Φ ≥ 0.4; medium, magenta, 0.2 < Φ < 0.4; and low, red, Φ ≤ 0.2). (a) The frontview of CAfn2 (the CAfn2 structure is oriented as in Figure 1). (b) The rear view of CAfn2.
Mentions: The CAfn2 Φ-values range from 0 to 0.5, indicating that none of thepositions analyzed is completely structured at the transition state(Table 2). In general, theΦ-values in the A and G-strands are close to 0, while those in the centralB, C, C′, E and F β-strands are higher, and the Φ-values in these centralstrands are higher in the central layers of the core than at the extremes(Figure 3), as observed inTNfn3,18 the tenth fnIII domain of fibronectin (FNfn10)16 and the titin immunoglobulin domain TI I27.17 The Φ-values were classified into low (Φ ≤ 0.2), medium (0.2 < Φ < 0.4) and high (Φ ≥ 0.4)classes. These Φ-values are mapped onto the CAfn2 structure in Figure 5.

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