Delineation and comparison of globular domains using HCA.

<p>The sequence is written on a duplicated alpha helical net and the hydrophobic amino acids (V, I, L, M, F, W, Y) are contoured <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003280#pcbi.1003280-Callebaut1" target="_blank">[14]</a>, <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003280#pcbi.1003280-Gaboriaud1" target="_blank">[15]</a>. These form hydrophobic clusters, which mainly correspond to regular secondary structures <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003280#pcbi.1003280-Woodcock1" target="_blank">[17]</a>. This is illustrated here with the chromo and chromo-shadow domains of the mouse chromobox homolog 1 (CBX1_MOUSE, UniProt P83917), for which the observed secondary and tertiary structures are shown below the HCA plot (pdb identifiers: 1AP0 and 1DZ1) <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003280#pcbi.1003280-Ye1" target="_blank">[66]</a>. Globular domains (boxed), containing approximately one third of hydrophobic amino acids gathered into clusters, are separated by a hinge, which is clearly less hydrophobic. The comparison of the HCA plots of the two domains indicates similar shapes of clusters (shaded green and red), suggesting a structural relationship. This potential relationship is further strengthened by sequence identities (shaded yellow) identified relative to the conserved positions of hydrophobic amino acids within clusters and is supported at the 3D level. The hydrophobic clusters shaded in green and red correspond to the internal strand beta2 and to the C-terminal alpha helix, respectively. In the chromo shadow domain, the loop linking strand beta3 and the C-terminal alpha helix includes a short alpha helix, containing two alanine residues.