Role of hydrophobic clusters and long-range contact networks in the folding of (alpha/beta)8 barrel proteins

Abstract

Analysis on the three dimensional structures of (alpha/beta)(8) barrel proteins provides ample light to understand the factors that are responsible for directing and maintaining their common fold. In this work, the hydrophobically enriched clusters are identified in 92% of the considered (alpha/beta)(8) barrel proteins. The residue segments with hydrophobic clusters have high thermal stability. Further, these clusters are formed and stabilized through long-range interactions. Specifically, a network of long-range contacts connects adjacent beta-strands of the (alpha/beta)(8) barrel domain and the hydrophobic clusters. The implications of hydrophobic clusters and long-range networks in providing a feasible common mechanism for the folding of (alpha/beta)(8) barrel proteins are proposed.

FIGURE 1

The 8-Å contact map for Taka amylase. β shows the presence of hydrophobic clusters at Y12, I60, T291, and I326 in β-strands; and α indicates the location of T239 in α-helix.

FIGURE 2

Long-range contact network in the hydrophobic clusters of Taka amylase. The circles denote hydrophobic clusters, and squares represent farthest long-range contacts. H, helix; S, strand; and C, coil.