PDBsum entry 1hyr

Immune system

PDB id: 1hyr

Contents

Protein chains

128 a.a. *

275 a.a. *

Waters ×46

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Complex structure of the activating immunoreceptor nkg2d and its mhc class i-Like ligand mica.

Authors

P.Li, D.L.Morris, B.E.Willcox, A.Steinle, T.Spies, R.K.Strong.

Ref.

Nat Immunol, 2001, 2, 443-451.

PubMed id

11323699

Abstract

The major histocompatibility complex (MHC) class I homolog, MICA, is a stress-inducible ligand for NKG2D, a C-type lectin-like activating immunoreceptor. The crystal structure of this ligand-receptor complex that we report here reveals an NKG2D homodimer bound to a MICA monomer in an interaction that is analogous to that seen in T cell receptor-MHC class I protein complexes. Similar surfaces on each NKG2D monomer interact with different surfaces on either the alpha1 or alpha2 domains of MICA. The binding interactions are large in area and highly complementary. The central section of the alpha2-domain helix, disordered in the structure of MICA alone, is ordered in the complex and forms part of the NKG2D interface. The extensive flexibility of the interdomain linker of MICA is shown by its altered conformation when crystallized alone or in complex with NKG2D.

Secondary reference #1

Title

Crystal structure of the mhc class I homolog mic-A, A gammadelta t cell ligand.

Authors

P.Li, S.T.Willie, S.Bauer, D.L.Morris, T.Spies, R.K.Strong.

Ref.

Immunity, 1999, 10, 577-584. [DOI no: 10.1016/S1074-7613(00)80057-6]

PubMed id

10367903

Figure 4.
Figure 4. Detailed Views of the “Latch” and the Crystallographic Dimer(A) Stereoview of a ribbon representation of the folds of MIC-A (blue) and HLA-B27 (green) in the region of helix 2b in the α2 domain highlighting the “latch.” The side chains of the latch residue (Val-95 in MIC-A and Gly-100 in HLA-B27) and the conserved disulfide bond (Cys-96/Cys-164) are shown in ball-and-stick representation.(B and C) A view from the side (B) and from the top (C) of the crystallographic dimer. The two MIC-A monomers, one in red and the other in blue, are shown as backbone ribbons. The ordered N-linked carbohydrate is shown in ball-and-stick representation, and the crystallographic dyad axis is indicated by the black oval. The C-termini of the two monomers are colored yellow.

Figure 5.
Figure 5. Space-Filling Representations of the Surface Character of MIC-A(A and B) A view of the back (A) and the side (B) of MIC-A highlighting the potential N-linked oligosaccharide sites present in all primate MIC alleles (orange) and those conserved in all primate MIC-A alleles (red). Residues shown in purple correspond to residues buried in a hypothetical complex with β[2]-m (see Figure 3).(C and D) Views of the equivalent of the peptide/TCR-binding surface of the platform domain (the “top,” [C]) and the β[2]-m binding surface of the platform domain (the “underside,” [D]; same orientation as in [A]) of MIC-A. Residues conserved across all primate MIC sequences are colored blue; residues where conservative substitutions have occurred (L/V/I, E/D, D/N, E/Q, E/N, or R/K) are colored green; nonconserved residues are colored yellow; residues in the α3 domain are colored gray. Two patches of conserved residues straddle the N-linked oligosaccharide at Asn-8: patch 1 (below Asn-8 in [D]): Ser-4, Arg-6, Glu-25, His-27, Gly-30, Gln-31, Pro-45, Trp-49, Glu-97, and Arg-180; patch 2 (above and to the left of Asn-8 in [D]); Leu-12, Lys-84, Leu-87, His-109, Tyr-111, Asp-113, Gly-114, Glu-115, Gln-131, and Ser-132. Residues at potential N-linked glycosylation sites are colored as in (A) and (B).

The above figures are reproduced from the cited reference with permission from Cell Press

Secondary reference #2

Title

Activation of nk cells and t cells by nkg2d, A receptor for stress-Inducible mica.

Authors

S.Bauer, V.Groh, J.Wu, A.Steinle, J.H.Phillips, L.L.Lanier, T.Spies.

Ref.

Science, 1999, 285, 727-729. [DOI no: 10.1126/science.285.5428.727]

PubMed id

10426993

Figure 2.
Fig. 2. Expression of a receptor for MICA on lymphocyte subsets. Two- and three-color flow cytometric analysis of freshly isolated PBLs (10). Upper four density plots show the indicated stainings of total PBLs; bottom two plots show stainings of gated CD3^+ T cells. Numbers in upper right fields indicate percentages of gated cells in quadrants. Similar results were obtained with PBLs from six healthy individuals and by using mAb 5C6. The low staining resolution in the CD56 plot was mainly due to large numbers of CD56^low cells.

Figure 4.
Fig. 4. Activation of effector cells by MICA engagement or ligation of NKG2D. (A) Expression of MICA sensitized Daudi- [2]m transfectants to lysis by NKL cells. Cytotoxicity was inhibited by anti-MICA (mAb 2C10) or anti-NKG2D (mAb 1D11). Anti-HLA-E mAb 3D12 restored lysis (4). (B) The anti-NKG2D mAbs 1D11 and 5C6 induced redirected lysis of mouse mastocytoma Fc R^+ P815 cells by NKL cells, by the 1B V[ ]1 T-cell clone, and by a peripheral blood CD8^+ T-cell clone (10). Data shown are representative of four and five T-cell clones, respectively. (C) Cytotoxicity of NKL cells against the HeLa (cervical), DU145 (prostate), HTB-78 (ovary), and SW480 (colon) tumor cell lines was decreased by anti-NKG2D mAb 1D11 or by F(ab')^2 fragments of the anti-MICA and anti-MICB mAb 6D4 but not by control IgG. Inhibitions were partial, as is often the case in antibody blocking. Data in (A) to (C) represent reproducible averages of three to five independent experiments and were obtained at an E:T of 10:1.

The above figures are reproduced from the cited reference with permission from the AAAs