The three-dimensional structure of an H-2L(d)-peptide complex explains the unique interaction of L-d with beta-2 microglobulin and peptide

Solution al: 2.5-Angstrom resolution of the three-dimensional structure of H-2L(d) with a single nine-residue peptide provides a structural basis for understanding its unique interaction with beta-2 microglobulin (beta(2)m) and peptide, Consistent with the biological data that show an unusually weal; association of L-d with beta(2)m, a novel orientation of the alpha 1/alpha 2 domains of L-d relative to beta(2)m results in a dearth of productive contacts compared with other class I proteins, Characteristics of the L-d antigen-binding cleft determine the unique motif of peptides that it binds, L-d has no central anchor residue due to the presence of several bulky side chains in its mid-cleft region, Also, its cleft is significantly more hydrophobic than that of the other class I molecules for which structures are known, resulting in many fewer a-bonds between peptide and cleft residues, The choice of Pro as a consensus anchor at peptide position 2 appears to be related to the hydrophobicity of the B pocket, and to the unique occurrence of Ile (which mirrors Pro in its inability to form Ii-bonds) at position 63 on the edge of this pocket, Thus, the paucity of stabilizing II-bonds combined with poor complementarity between peptide position 2 Pro and the B Docket contribute to the weak association between L-d and its peptide antigen, The unique structural interactions of L-d with beta(2)m acid peptide could make L-d more suited than other classical class I molecules to play; a role in alternative pathways of antigen presentation.