Convergence on a distinctive assembly mechanism by unrelated families of activating immune receptors.
Activating receptors in cells of hematopoetic origin include members of two unrelated protein families, the immunoglobulin (Ig) and C type lectins, which differ even in the orientation of the transmembrane (TM) domains. We examined assembly of four receptors with diverse function: the NK receptors KIR2DS and NKG2C/CD94, the Fc receptor for IgA, and the GPVI collagen receptor. For each of the four different receptors studied here, assembly results in the formation of a three-helix interface in the membrane involving two acidic TM residues from the signaling dimer and a basic TM residue from the ligand recognition module, an arrangement remarkably similar to the T cell receptor (TCR)-CD3 complex. The fact that the TM domains of Ig family and C type lectins adopt opposite orientations proves that these receptor families independently evolved toward the same structural arrangement of the interacting TM helices. This assembly mechanism is thus widely utilized by receptors in cells of hematopoetic origin.
Feng
Jianwen
J
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Garrity
David
D
Call
Matthew E
ME
Moffett
Howell
H
Wucherpfennig
Kai W
KW
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001773:Blood Cells / Q000737:chemistry / Q000276:immunology; D019281:Dimerization; D007070:Immunoglobulin A / Q000737:chemistry / Q000235:genetics; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry / Q000235:genetics; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D055654:NK Cell Lectin-Like Receptor Subfamily C; D038981:Receptors, Collagen / Q000737:chemistry / Q000235:genetics; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D054340:Receptors, KIR; D055607:Receptors, Natural Killer Cell; D016415:Sequence Alignment; D015854:Up-Regulation
D048868:Adaptor Proteins, Signal Transducing; D007070:Immunoglobulin A; D007141:Immunoglobulin Fc Fragments; C433932:KIR2DS2 protein, human; C527060:Klrc2 protein, mouse; D008565:Membrane Proteins; D055654:NK Cell Lectin-Like Receptor Subfamily C; D038981:Receptors, Collagen; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D055607:Receptors, Natural Killer Cell; C110546:TYROBP protein, human