Invariant chain made in Escherichia coli has an exposed N-terminal segment that blocks antigen binding to HLA-DR1 and a trimeric C-terminal segment that binds empty HLA-DR1.
Invariant chain (Ii), a membrane glycoprotein, binds class II major histocompatibility complex (MHC) glycoproteins, probably via its class II-associated Ii peptide (CLIP) segment, and escorts them toward antigen-containing endosomal compartments. We find that a soluble, trimeric ectodomain of Ii expressed and purified from Escherichia coli blocks peptide binding to soluble HLA-DR1. Proteolysis indicates that Ii contains two structural domains. The C-terminal two-thirds forms an alpha-helical domain that trimerizes and interacts with empty HLA-DR1 molecules, augmenting rather than blocking peptide binding. The N-terminal one-third, which inhibits peptide binding, is proteolytically susceptible over its entire length. In the trimer, the N-terminal domains act independently with each CLIP segment exposed and free to bind an MHC class II molecule, while the C-terminal domains act as a trimeric unit.
D000595:Amino Acid Sequence; D000944:Antigens, Differentiation, B-Lymphocyte / Q000737:chemistry* / Q000378:metabolism; D001483:Base Sequence; D003593:Cytoplasm / Q000737:chemistry; D017931:DNA Primers / Q000737:chemistry; D004926:Escherichia coli; D015798:HLA-DR1 Antigen / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry; D008969:Molecular Sequence Data; D009038:Motion; D010446:Peptide Fragments / Q000737:chemistry; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry; D012995:Solubility
D000944:Antigens, Differentiation, B-Lymphocyte; D017931:DNA Primers; D015798:HLA-DR1 Antigen; D000949:Histocompatibility Antigens Class II; D008565:Membrane Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C045084:invariant chain