Figure 2: Structure of farnesylated PEX19 CTD.

(a) Cartoon representation of farnesylated PEX19 CTD. The farnesyl binding site is formed by residues in helix α1 (cyan), helices α2-α4 (blue), the lid region (residues 262–283; violet) and the CaaX box (orange). The farnesyl is drawn as sticks in magenta. (b) Surface representation of the farnesylated PEX19 CTD coloured by hydrophobicity. The hydrophobic surface region comprising helix α1 and the lid is indicated by a black dotted line. (c) Two different views of the farnesyl recognition site. Dashed lines indicate intermolecular NOE correlations, collected on PEX19 farnesylated samples using various labelling schemes on the protein side. The relative position of helices in the PEX19 CTD fold surrounding the farnesyl is indicated. (d) Comparison of the crystal structure of the PEX19 CTD lacking the C-terminal 16 residues (CTDΔC, left)²¹, with the solution structure of the farnesylated PEX19 CTD (right). Structural changes of the lid region are highlighted by a red box. (e) The structure of the core helical bundle comprising helices α2-α4 is highly similar while the orientation of helix α1 (cyan) differs. The lid (residues 262–283) covers the farnesyl group in farnesylated PEX19 CTD (violet), while in the crystal structure of non-farnesylated PEX19 CTDΔC these residues occupy the farnesyl binding cavity (orange). Note, that residues 283–299 in the NMR structure and loop regions connecting the helices have been omitted for clarity. (f) Large conformational changes of the lid induced by PEX19 farnesylation are indicated by change in the Cα atom positions of lid residues with the helical core domain superimposed as in e. Error bars indicate the s.d. for the 20 models of the NMR ensemble. The largest changes are highlighted by a red box as in d.