The Origins of Specificity in Polyketide Synthase Protein Interactions
Figure 3
In this figure, symbols associated with head domains are colored red, and those associated with tail domains are colored green. This coloring is unrelated to compatibility class, as all domains pictured belong to compatibility class H1–T1.
(A,B) CRoSS matrices, showing the residue pairs that significantly contribute to specificity (Methods). Residues on the C-terminal head domain are indexed vertically (i = 1, ... , 19); residues on the N-terminal tail domain are indexed horizontally (j = 1, ... , 27). Each entry shows -log10(ρij) for the corresponding site-pair, with the scale indicated on the color bar; the higher this value, the more significant the site-pair as a determinant of specificity.
(A) The H1–T1 control matrix, generated by comparing random pairings with noninteractors. Since we expect no significant hits, these entries provide us with an estimate of the random background.
(B) The H1–T1 interaction matrix, generated by comparing interactors with noninteractors. Several entries are highlighted above the background (white circles serve as guides to the eye). The matrix is sparse, showing that residue pairs at a few key sites vary independently, uncorrelated to any broad phylogenetic patterns. There are only seven significant residue pairs (Figure S1C). These are, in order of significance, {i, j} = {6,5}, {13,11}, {12,18}, {12,11}, {12,12}, {12,16}, {12,5}. The three head residues and five tail residues that make up these pairs are indicated along the axes by red and green arrows, respectively.
(C) Representative multiple-sequence alignments of H1 head domains (left) and T1 tail domains (right), with cartoon representations of the head and tail domains shown below. Each row shows an interacting head–tail pair, labeled by the PKS pathway it belongs to, and the interface number within that pathway. The three head residues and five tail residues selected by CRoSS are indicated by red and green arrows, respectively; the corresponding positions in the sequence alignments are highlighted in bold. The three most significant head and tail residues (used to define code words in Figure 4) are indicated by asterisks. The head and tail alignments are divided into four groups each (H1a–H1d and T1a–T1d) corresponding to the subclasses discussed in Figure 4.