The three-dimensional structure of a class I major histocompatibility complex molecule missing the α3 domain of the heavy chain

Abstract

Class I major histocompatibility complex (MHC) molecules are ternary complexes of the soluble serum protein β2-microglobulin, MHC heavy chain, and bound peptide. The first two domains (α1, α2) of the heavy chain create the peptide binding cleft and the surface that contacts the T-cell receptor. The third domain (α3) associates with the T-cell co-receptor, CD8, during T- cell recognition. Here we describe the x-ray crystal structure of a human class I MHC molecule, HLA-Aw68, from which the α3 domain has been proteolytically removed. The resulting molecule shows no gross morphological changes compared to the intact protein. A decameric peptide complexed with the intact HLA-Aw68 is seen to bind to the proteolized molecule in the conventional manner, demonstrating that the α3 domain is not required for the structural integrity of the molecule or for peptide binding.