Figure 1 - full size


Figure 1.
Fig. 1. The crystal structure of DQ0602-hypocretin. (A) The solvent-accessible surface of the DQ0602 peptide binding groove is colored by electrostatic potential (blue, positive charge; red, negative charge) viewed onto the TCR recognition surface. The residues of the peptide are shown as ball-and-stick in atomic coloring (blue, nitrogen; red, oxygen; yellow, peptide carbon). The major pockets within the groove are labeled in the standard MHC class II nomenclature. (B) A composite omit map contoured at 1 is shown in blue chicken wire. The peptide is depicted in ball-and-stick colored as in A and viewed through the 1-helix. (C) A superposition of the peptides from the DQ0602-hypocretin and DQ0302-insulinB structures. The peptides are shown with atomic coloring as in A except for the insulinB peptide carbon atoms (green). The view is as in B, and the residues are labeled in the standard MHC class II nomenclature. (D) Superposition of the DQ0602 and DQ0302 peptide binding grooves. The C traces for DQ0602 (gray) and for DQ0302 (green) are viewed as in A. The well ordered residues of the hypocretin peptide and linker are shown with atomic coloring (peptide coloring as in A; orange, linker carbon). Residues 46 to 55 and 85 to 91 show significant main chain and side chain conformational changes between the two MHC class II structures. The C positions of these residues in DQ0602 are indicated by spheres (blue, -chain; magenta, -chain). The concerted conformational changes impact on the P1 pocket (see text) and on the heterodimer interface. In particular, residue 48 changes from leucine in DQ0302 to tryptophan in DQ0602, and the side chain of Trp-48 (shown in blue sticks) is reoriented to form a tight, hydrophobic interaction at the interface with the 2 domain.