Figure 2. Structures of the KDEL receptor bound to HDEL and RDEL retrieval signals.

(a) Crystal structure of chicken KDELR2 viewed from the side with the transmembrane helices numbered and coloured from N-terminus (blue) to C-terminus (red). The predicted membrane-embedded region of the receptor is indicated by a grey shaded box, with labels at the luminal and cytoplasmic faces. The TAEHDEL peptide is shown in stick format, coloured grey. (b) Close up views of bound TAEHDEL (this study), (c) TAERDEL (this study), and (d) TAEKDEL (PDB:6I6H) peptides bound to the receptor are shown with contributing side chains labelled. Hydrogen bonds are indicated as dashed lines. The molecular orbitals of W120 and the −4 histidine on the peptide are shown as a dotted surface. (e) Superposition of the HDEL, RDEL, and KDEL peptides reveals near identical binding position within the receptor. Retrieval signal side chains are numbered counting down from the C-terminus.

Figure 2—figure supplement 1. Analysis of pH-dependent interaction of HDEL, KDEL, and RDEL signals with KDELR2.

Thermal stability of chicken KDEL2 was measured at pH 5.4, 5.9, 6.4, and 7.0 in the presence of TAEHDEL, TAEKDEL, and TAERDEL peptides. The difference in melting temperature to a no ligand control is plotted in the bar graph as mean ± SEM (n = 3).

Figure 2—figure supplement 2. Polder difference density electron density maps for HDEL and RDEL peptides.

(a) The structure of the KDELR bound to the TAEHDEL peptide is shown as in Figure 2a. The mFo-DFc difference electron density used for model building is displayed (green mesh), contoured at 3σ. (b) Equivalent maps calculated for the RDEL peptide.