Fig. 2

Structure of the band 4.1/JEF domain (HCA). (A) HCA plots of a conserved region of the 4.1/JEF domain, defined by two highly conserved blocks (blocks 6 and 7), from JAK (JAK1_HUMAN, Swiss-Prot accession number P23458), FAK (FAK1_HUMAN, Swiss-Prot accession number Q05397), and ezrin (EZRI_HUMAN, Swiss-Prot accession number P15311). The sequence of human KIAA0316 (GenBank accession number AB002314) is also shown, as it appears to be a key linker between FAK and classical 4.1 domains. Sequence identities (white on a black background) are associated with cluster similarities (shaded gray), indicating the conservation of a similar 2D environment. Note that the intervening sequences linking conserved blocks (horizontal arrows) are of considerable variable length. The basic principles of HCA plots are indicated in the inset: the amino acid sequence (obliquely from top to bottom and left to right, 1D) is shown on a duplicated α-helical net (18). Hydrophobic residues are boxed and form clusters that correspond mainly to the internal sides of regular secondary structures (α helices and β strands), oriented toward the hydrophobic core of globular proteins. Inspection of the plot from left to right allows identification and comparison of those patterns indicative of secondary structure (inset, 2D). Special symbols used for proline (pro), glycine (gly), serine (ser) and threonine (thr) are indicated. (B) HCA plot of the 4.1/JEF domain (residues 1–295) of human ezrin (EZRI_HUMAN, Swiss-Prot accession number PI5311). The plot is divided into three parts. The central hinge containing Tyr-145 (Y*), a substrate for tyrosine kinases, is set aside to highlight the similarities between the two aligned subdomains (residues 1–132 and 168–295). Secondary structure predictions are shown below the duplicated subdomains. Sequence identities (white on a black background) are associated with cluster similarities (shaded gray), indicating the conservation of a similar 2D environment. Special symbols used for proline, glycine, serine, and threonine are as indicated in panel A.