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Communicated by Peter Doherty, University of Melbourne, Victoria, Australia, December 30, 2004 (received for review December 21, 2004)
Abstract
HLA-G is a nonclassical major histocompatibility complex class I (MHC-I) molecule that is primarily expressed at the fetal–maternal interface, where it is thought to play a role in protecting the fetus from the maternal immune response. HLA-G binds a limited repertoire of peptides and interacts with the inhibitory leukocyte Ig-like receptors LIR-1 and LIR-2 and possibly with certain natural killer cell receptors. To gain further insights into HLA-G function, we determined the 1.9-Å structure of a monomeric HLA-G complexed to a natural endogenous peptide ligand from histone H2A (RIIPRHLQL). An extensive network of contacts between the peptide and the antigen-binding cleft reveal a constrained mode of binding reminiscent of the nonclassical HLA-E molecule, thereby providing a structural basis for the limited peptide repertoire of HLA-G. The α3 domain of HLA-G, a candidate binding site for the LIR-1 and -2 inhibitory receptors, is structurally distinct from the α3 domains of classical MHC-I molecules, providing a rationale for the observed affinity differences for these ligands. The structural data suggest a head-to-tail mode of dimerization, mediated by an intermolecular disulfide bond, that is consistent with the observation of HLA-G dimers on the cell surface.
The class I major histocompatibility complex (MHC-I) encodes the classical (class Ia) and nonclassical (class Ib) molecules (1–3). These molecules contain a membrane-spanning heavy chain (hc) that is noncovalently associated with β2-microglobulin (β2M) (1). Peptide antigens are bound within the antigen-binding cleft formed by the α1 and α2 domains of the hc, whereas the α3 domain can bind coreceptors (4). Class Ia molecules are characterized by a significant number of polymorphisms, many of which are clustered around the antigen-binding cleft (1, 2), that determine binding motifs for individual MHC-I molecules (5). The class Ib HLA-E, -F, and -G genes show limited allelic variation (6, 7) compared with class Ia genes (3, 6, 8). Although little is known about HLA-F, HLA-E interacts with CD94/NKG2A on the surface of natural killer cells, thereby inhibiting activation (9–11). A striking feature of HLA-G is its particular expression on the fetal trophoblast cells that invade the maternal endometrium during placenta formation (12–14). Although the precise in vivo function of HLA-G in the placenta is unknown (15), indirect evidence suggests that it plays a role in maternal tolerance of the fetus by mediating protection from the deleterious effects of natural killer cells, cytotoxic T lymphocytes, macrophages and mononuclear cells (14, 16–19). There is evidence that HLA-G interacts with the inhibitory receptors LIR-1 (leukocyte Ig-like receptor 1 or ILT2) and LIR-2 (leukocyte Ig-like receptor 2 or ILT4) that can be expressed by monocytes, macrophages, cytotoxic T lymphocytes, and natural killer cells (20, 21). KIR2DL4 (killer Ig-like receptor 2DL4) also may interact with HLA-G, although the data are controversial (14, 22). LIR-1 and -2 interact with the α3 domain of multiple class I molecules (14, 22). Interestingly, both LIR-1 and -2 bind to HLA-G with higher affinity than to classical MHC molecules (23), suggesting that differences in the α3 domain are important for LIR-1/2 affinity (24). However, the structural correlates of this difference in affinity have not previously been reported.
HLA-G mRNA transcripts produce up to seven different isoforms of the HLA-G molecule (14, 25, 26), the functions of which are unclear (15) but theoretically could involve modulation of leukocyte activity at the fetal–maternal interface (27, 28). Full-length HLA-G1 is expressed as a cell surface glycoprotein, some of which appears to be a disulfide-bonded homodimer that is cross-linked by the cysteine position 42 (Cys-42) of the hc (29, 30). HLA-G associates with the peptide-loading complex in the endoplasmic reticulum (30–32) but also binds some signal sequence-derived peptides in a transporter associated with antigen processing (TAP)-independent fashion (31). HLA-G binds nonamer peptides from intracellular proteins with a defined peptide-binding motif (13, 31, 33). The diversity of peptides bound by HLA-G is restricted relative to class Ia molecules but diversified relative to HLA-E (13, 31). In the placenta, the HLA-G peptide repertoire is even more restricted with a single peptide accounting for ≈15% of all recovered ligand (13). The structure of HLA-G explains its restricted peptide repertoire, provides a potential mode for disulfide-bonded dimerization, and suggests a structural basis for the higher affinity of LIR-1 and -2 for HLA-G compared with other MHC-I molecules.
Materials and Methods
Cloning, Expression, and Crystallization of HLA-G. Details pertaining to the cloning, expression, and crystallization of HLA-G will be published elsewhere (C.S.C., L.K.-N., L.K., J.R., and J.M., unpublished data). Briefly, the gene encoding HLA-G*0101 was cloned from the human choriocarcinoma cell line JEG-3 by using standard protocols (32). Another form of HLA-G*0101 also was made, in which the codon for Cys-42 was changed to encode serine by QuikChange site-directed mutagenesis (Stratagene). The two forms of HLA-G1 were expressed separately in BL21 Escherichia coli, and inclusion body protein was prepared, refolded, and purified essentially as described in ref. 34.
Data Collection, Structure Determination, and Refinement. A 1.9-Å data set was collected from a flash-frozen crystal at the BioCars beamline (Advanced Photon Source, Chicago) by using a Quantum 4 charge-coupled device detector. The data were processed and scaled by using the hkl package (HKL Research, Charlottesville, NC; Table 1). The crystal structure of the HLA–G/RIIPRHLQL complex was solved by using the molecular replacement method, as implemented in the amore package (35), using the unliganded HLA-E structure (36) (Protein Data Bank ID code 1MEH) as the search model. For the search model, all differences were mutated to alanine, water molecules were removed, and bound peptide was removed. Unbiased features in the initial electron density map confirmed the correctness of the molecular replacement solution. The progress of refinement was monitored by the R free value (4% of the data) with neither a σ nor a low-resolution cutoff being applied to the data. The structure was refined by using the simulated-annealing protocol implemented in cns (Version 1.0; ref. 37), interspersed with rounds of model building by using the program o (38). Tightly restrained individual B factor refinement was used, and bulk solvent corrections were applied to the data set. H-bonds were located by using programs from the ccp4 package (contacts). The final 1.9-Å model, which comprises residues 2–276 (hc), 1–99 (β2M), 1–9 (peptide), one cobalt ion, and 430 water molecules, has an R fac of 23.5% and R free of 26.4% (see Table 1 for statistics). Coordinates have been deposited in the Protein Data Bank (ID code 1YDP).
View this table:
Table 1.
Data collection and refinement statistics
Results
Structural Overview. We have determined, to 1.9-Å resolution, a variant of HLA-G in which Cys-42 of the hc was mutated to Ser to improve the yield of correctly folded HLA-G. Diffracting crystals (0.2 × 0.2 × 0.2 mm) were obtained by using the hanging drop vapor diffusion technique at 4°C by using 22% polyethylene glycol (pH 6.8) as the precipitant. The crystals belong to space group P3221 with unit cell dimensions a = b = 77.15 Å, and c = 151.72 Å. A Cys-42 represents a unique feature of HLA-G when compared with other MHC-I molecules. HLA-G has a propensity to dimerize, by means of Cys-42 disulfide bond formation, on the cell surface (29). The crystal packing is not suggestive of a higher-order oligomeric assembly within the lattice. Moreover, crystals of wild-type HLA-G also were grown under identical conditions to that of the mutant and exhibited identical unit cell dimensions, revealing that HLA-G does not dimerize under these crystallization conditions (data not shown). However, the solvent-exposed position of residue 42 in the HLA-G structure (Fig. 1A ) suggests that an intermolecular disulfide bond is possible.
Fig. 1.
Overview of the structure of HLA-G. (A) The hc is shown in purple, β2M in blue, and the peptide in green. The position of the Cys-42 → Ser mutation is labeled. (B) Conformation of bound peptide. The corresponding 2F o - F c electron density is shown in mesh format. The peptide is in ball-and-stick format with each amino acid labeled.
The overall structure of HLA-G is similar to MHC-I molecules, namely, a hc comprising three domains (α1, α2, and α3) that is noncovalently associated with β2M (Fig. 1). We compared the structure of HLA-G with HLA-E and the murine nonclassical Qa-2, as well as representative structures of the classical HLA-A, -B, and -C alleles. HLA-G shares significant sequence similarity to Qa-2 (78%), HLA-E (78%), HLA-A2 (82%), HLA-B44 (80%), and HLA-CW3 (84%) (Fig. 2). When comparing HLA-G with both classical and nonclassical MHC structures, there was no overt difference in the juxtaposition of the domains of the hc and with respect to the β2-m domain. The rms deviation for the pairwise superpositions between HLA-G and Qa-2, HLA-E, HLA-A2, HLA-B44, and HLA-CW3 was 0.86, 0.94, 0.94, 0.89, and 1.21 Å over all atoms, respectively (see Table 2, which is published as supporting information on the PNAS web site). These pairwise structural superpositions reveal that some of the most significant structural differences are clustered around the antigen-binding cleft and the LIR-1/2 binding site reflecting the sequence differences between HLA-G and the other MHC-I alleles (Fig. 2).
Fig. 2.
Sequence alignment of human HLA-G with HLA-E, -A2, -B44, and -CW3 as well as mouse Qa-2. The sequence alignment is divided into the three domains: α1, α2, and α3. Residues highlighted with red have 100% identity. Residues highlighted in yellow are conservatively substituted. The secondary structure of HLA-G is illustrated directly above the sequence alignment. Orange arrows indicate β-strands, and blue cylinders indicate α-helices. Residues directly interacting with the peptide are marked with a large green star, and residues interacting only via a water molecule are marked with a hollow circle (see Table 3). The loop in domain α3 involved in LIR-1/2 (ILT-2/4) binding is highlighted with a green box.
Constrained Peptide Conformation. The RIIPRHLQL peptide, a natural ligand of HLA-G from histone H2A protein (31), was bound in a groove formed by the α1 and α2 helices with a floor formed by an antiparallel β sheet (Figs. 1B and 3). The electron density for the peptide, and the contacting residues, was unambiguous. The peptide makes extensive polar and nonpolar contacts with HLA-G (see Table 3, which is published as supporting information on the PNAS web site), totaling 2 salt bridges, 17 hydrogen (H) bonds, and 16 water-mediated H-bonds as well as a large number of van der Waals contacts. The bound peptide adopts an extended conformation, anchored at both the N and C termini with a bulged region, centered at Pro-4, that projects out of the binding groove (Figs. 1B and 3).
Fig. 3.
Comparison of MHC-I bound peptides. The conformations of peptides bound by HLA-G (purple), HLA-E (48) (red), HLA-A2 (49) (yellow), and Qa-2 (39) (green) are shown in a side view (A), top view (B), and a view showing the main chain interactions between the epitope and the HLA-G hc (C). Polar interactions are depicted only (dashed lines); water molecules are shown in blue spheres.
Of these interactions, 13 H-bonds and 10 water-mediated H-bonds are mediated via the peptide backbone (Table 3 and Fig. 3C ). The P1-Arg backbone is anchored by H-bonds to Tyr-7, Tyr-159, and Tyr-171 (Fig. 3C ), a H-bonding network that is found in class Ia MHC, as well as HLA-E (36) and Qa-2 (39). In addition, the Glu-63 H-bond to the P2 amide group, present in most class Ia complexes, Qa-2 and HLA-E, is also present in HLA-G (Fig. 3C ). The carboxylate of the PΩ residue (the C-terminal amino acid) is also anchored by a well conserved H-bonding network involving Tyr-84, Ser-143, and Lys-146 and water-mediated interactions with Thr-73, Asn-77, and Thr-80 (Fig. 3C ). Again, this interaction network is generally well conserved in MHC-I complexes. There is notable variation in the interactions with the P8 and P9 main chain between the MHC-I allotypes that is largely attributable to sequence differences at positions 77 and 147 from the α1 and α2 helix, respectively (see Fig. 2, sequence alignment). In HLA-G, these positions are occupied by Asn-77 and Cys-147; in HLA-E, they are occupied by Asn-77 and Ser-147, whereas in most class Ia structures (and Qa-2), position 147 is occupied by a Trp that H-bonds to the main chain at P8. The smaller residue at position 147 in HLA-G does not interact with the peptide, analogous to that observed in HLA-E (36). Also resembling HLA-E, the Asn-77 in HLA-G H-bonds to the carbonyl of P-7 Leu and the amide of P-9 (Fig. 3C), whereas in MHC-Ia structures, the polymorphic residue at position 77, only interacts with P-9 (40–42).
In addition to the tethering of the N and C termini, the central region of the peptide backbone also is involved in a significant number of interactions. For example, P4-Pro H-bonds to His-70, an interaction that is unique when compared with the classical and nonclassical MHC-I structures (40) (Fig. 3C ). Interestingly, the P4-Pro appears to play a significant structural role in maintaining the bulged conformation of the peptide rather than direct specificity-governing interactions with HLA-G, because the P4-Pro side chain forms minimal contacts with the HLA-G (Figs. 1B and 3C ). In addition, the main chain atoms of P3-Ile, P5-Arg, P6-His, and P7-Leu also are involved in interacting with HLA-G, either directly or via a well ordered water-mediated network (Fig. 3C ).
Collectively, these contacts along the length of the epitope are partly responsible for the conformation of the epitope bound to HLA-G, which is atypical of MHC-Ia structures, and more reminiscent of that observed in HLA-E (Fig. 3 A and B ).
Structural Basis for Restricted Peptide Specificity. The constrained conformation of the epitope with its minimal protrusion from the cleft is also attributable to the contacts the peptide side chains make to the HLA-G. Six of the peptide side chains, P1-Arg, P2-Ile, P3-Ile, P6-His, P7-Leu, and P9-Leu, make a number of contacts with the HLA-G (Fig. 4 A–C ), whereas Pro-4, Arg-5, and Gln-8 are highly solvent exposed (Fig. 1B ). The HLA-G interacting side chains of the peptide are predominantly hydrophobic, and correspondingly the peptide-binding groove of HLA-G is notably hydrophobic (Fig. 4D ). The peptide binding groove of HLA-G most closely resembles that of HLA-E, where the conformation of the bound peptides are very similar (Fig. 3 A and B ) (with rms deviation of 0.49 Å; see Table 2); there is significantly more variation in the conformation of the bound peptide compared with the other MHC-I molecules (rms deviation 1.00–1.56 Å; see Table 2 and Fig. 3 A and B ).
Fig. 4.
Pocket-mediated interactions of HLA-G. HLA-G residues are shown in purple, peptide residues are shown in green, polar contacts are depicted as dashed lines, and water molecules are shown as blue spheres. (A) Pockets A and B mediating interactions with P1-Arg and P2-Ile, respectively. (B) Pockets C and D mediating interactions with P6-His and P2-Pro, respectively. (C) Pockets E and F mediating interactions with P7-Leu and P9-Leu, respectively. (D) Overview of the hydrophobic nature of the HLA-G binding cleft. Hydrophobic regions of the cleft that bind peptide are shown in green with the important anchor residue His-70 colored yellow. The pockets are labeled A–F, and the peptide is depicted as a ball-and-stick structure.
As with MHC-I molecules, the RIIPRHLQL peptide is accommodated in the peptide-binding groove by a series of pockets (Fig. 4). Pool sequencing of endogenous HLA-G peptide ligands has identified putative conserved anchor residues comprising a leucine at the C terminus and proline or small hydrophobic residue at P3, followed by a proline or glycine at P4 (13, 31, 33). Either leucine or isoleucine is found at P2 and there is a preference for a positively charged residue at P1 and an aromatic residue at P6. The restriction of the P1 residue is explained by the interactions of the P1-Arg side chain within the A pocket, which is closed at the N terminus of the peptide by Trp-167, (Fig. 4A ). The structure of this pocket is similar to both HLA-E (36) and HLA-A2 (43); however, in Qa-2 the residue at position 167 is a serine leading to a wider open-ended pocket (39). The P1-Arg salt bridges to Glu-62 and Glu-63; moreover, the aliphatic moiety of the P1-Arg is further anchored by van der Waals interactions with Tyr-59 and Trp-167 (Fig. 4A ).
The B pocket is deep and hydrophobic, a feature common to a number of MHC-I molecules. The pocket is lined by Met-45, Ala-24, Tyr-7, Thr-67, His-70, and Trp-97 (Fig. 4A ). The hydrophobic characteristics of the B-pocket are consistent with the selection of a Leu/Ile peptide side chain at P2. In other MHC-I molecules, hc residue 9 is occupied by larger side chains such as histidine (HLA-E, HLA-B27, and Qa-2), phenylalanine (HLA-A2), and tyrosine (HLA-B44). However this residue is replaced by a Ser in HLA-G and as such does not participate in B-pocket interactions, but instead lies at the floor of the C-pocket that accommodates the P6-His (Figs. 2 and 4B ). The substitution of a Ser-9 creates a deeper pocket to accommodate the P6-His, which points into the peptide-binding groove and is involved in a network of interactions. The P6-His H-bonds to Asp-74 and His-70, forms water-mediated H bonds to Ser-9, Leu-95, Trp-97, Tyr-116, and Arg-156, and forms van der Waals contacts with His-70 and Trp-97 (Fig. 4B ). The pocket also is lined by Phe-22 and Tyr-116, and bulkier aromatics at the P6-position also may favorably interact with these residues. The P6-His/His-70 pairing is unusual; however, the extensive polar network, centered around P6-His, presumably provides a favorable environment for this His/His interaction to occur (44). HLA-E also possesses an unusual His/His pairing (His-9/His-99) at the floor of the cleft that also is involved in an intricate H-bonding network (36). Analogous to HLA-E and Qa-2, the C pocket is more hydrophobic than the classical MHC-I molecules, where Trp-97 replaces the charged Arg-97 found in many class Ia structures. Trp-97 also lies at the base of the relatively shallow D pocket in HLA-G, which accommodates the P3-Ile. HLA-G has a preference for proline or a small hydrophobic residue at P3, and the structural basis for this preference lies in hydrophobic interactions being made with Tyr-159, Trp-97, and Ile-99. The presence of Ile-99 compared with tyrosine in Qa-2 and HLA-A2, or histidine in HLA-E, creates a somewhat deeper D pocket.
P7-Leu resides within the E pocket, making van der Waals contacts with Tyr-116, Arg-156, Trp-133, Val-152, and Cys-147. Similar to HLA-E (Ser-147), the E pocket of HLA-G is deeper than the corresponding pocket in HLA-A2. However, the presence of Arg-156 in HLA-G serves to narrow this pocket, compared with other MHC-I molecules.
The PΩ Leu anchor residue is firmly seated in the hydrophobic F pocket lined by Leu-81, Asn-77, Leu-95, Tyr-116, Tyr-123, and Leu-124, analogous to the ligation of the PΩ Leu preferred by HLA-E. Leu-81 encloses this pocket at the C terminus of the HLA-G-bound peptide as occurs in HLA-A2 and HLA-E, whereas in Qa-2 this position is occupied by an alanine that provides a more spacious F pocket (36).
LIR-1 and LIR-2 Binding to HLA-G. The crystal structure of HLA-A2 bound to LIR-1 maps the binding site to residues 193–196, 198, and 248 of the α3 domain of the hc and residues 1–4, 85–89, and 91–94 of β2M (24, 45) (Fig. 5A ). The conformation and sequence composition of the 193–198 loop differs markedly between HLA-G and other MHC-I molecules. Positions 195 and 197 are occupied by phenylalanine and tyrosine, respectively, in HLA-G, and serine and histidine in other MHC-I molecules. The increased hydrophobicity of this region of HLA-G, relative to other MHC-I molecules, is likely to contribute to the higher affinity of HLA-G for LIR-1, such that they can potentially compete with CD8 for MHC-I binding. Thus, HLA-G binding of LIR-1/2 receptors may exert an inhibitory function by interfering with CD8-mediated, as well as LIR-1/2-mediated, inhibition (23).
Fig. 5.
HLA-G may bind to LIR-1 (ILT-2) with enhanced affinity and undergo disulfide-bond-mediated dimerization. (A) Comparative analysis of the candidate ILT-2 binding site on the α3 domain of HLA-G (purple) and the equivalent binding site on HLA-A2 (yellow). (B) Model of the HLA-G dimer, looking down onto the antigen-binding cleft; peptides are in red (A protomer, light gray) and pink (B protomer, dark gray). The dimerization site is mediated via an intermolecular Cys-42–Cys-42 disulfide, indicating that the protomers within the dimer cannot adopt a side-by-side arrangement. However, a head-to-tail HLA-G dimer would satisfy the requirements for a Cys-42-mediated dimer, in which the loops containing the Cys-42 would clasp onto each other. In this plausible configuration, intermolecular interactions mediated via the β2M domains are possible. LIR-1 has been solved in complex with HLA-A2 (Protein Data Bank ID code 1P7Q), in which the LIR-1 binding site onto the α3 domain of the hc was mapped. Given the similarities between HLA-G and HLA-A2, the molecular organization of the HLA-G/ILT2 complex can be postulated in this HLA-G dimeric arrangement (ILT2 in blue and cyan).
Discussion
A unique functional role for HLA-G is implied by its extraordinary expression in the placenta, unusual promoter elements (26), and limited peptide repertoire (13, 31). HLA-G has the highest sequence identity to HLA-Cw3 but nevertheless shows the highest degree of overall structural-relatedness to the murine homologue, Qa-2 (46). Surprisingly, the peptide-binding groove of HLA-G most closely resembles HLA-E, with an extensive network of contacts revealing the hybrid class Ia/Ib properties of the HLA-G molecule. This bonding network constrains the identity of peptides capable of binding HLA-G compared with classical MHC molecules in which the peptide sequence is fixed at only two or three anchor positions (40). As with HLA-E (36), the side chains of the residues at positions P2, P3, P6, P7, and P9 lie within well defined pockets in the peptide-binding groove; however, the P6 pocket of HLA-G must accommodate bulky side chains such as phenylalanine or histidine. Two of the preferred side chains identified in HLA-G ligands, the positively charged P1 residue and Pro at P4, are solvent exposed and appear to stabilize the HLA-G molecule rather than form hc contacts directly involved in binding. HLA-G acquires most of its peptide cargo after incorporation into the tapasin-dependent, peptide-loading complex containing the thiol oxido-reductase ER57, involved in disulfide bond rearrangements (30). This finding is consistent with the chaperone-assisted optimization of the constrained ligand repertoire of HLA-G, but it also could reflect a role for ER57 in HLA-G dimerization (29).
HLA-G is proposed to contribute to immunological tolerance of the fetus, making the interaction of HLA-G with inhibitory natural killer and LIR-1/2 receptors a matter of great interest. Although an interaction between KIR2DL4 and HLA-G has been reported (22), the interaction is not essential for reproduction (47) and remains controversial (14).
HLA-G binds the inhibitory LIR-1/2 molecules via β2M and the hc α3 domain (24, 45). In HLA-G, positions 195 and 197 of the α3 domain are occupied by phenylalanine and tyrosine, respectively, compared with serine and histidine in other MHC-I molecules. This altered structure and increased hydrophobicity may be the basis for the higher affinity of HLA-G for LIR-1 compared with other MHC-I molecules. In addition, the capacity of HLA-G to form disulfide-linked homodimers (29) might theoretically enhance the avidity of HLA-G for the LIR-1 and -2 receptors. In modeling the disulfide-bonded HLA-G homodimer, the two HLA-G protomers are oriented head-to-tail, creating an interaction between adjacent β2M molecules that potentially could allow enhanced HLA-G function through oligimerization of LIR-1/2 receptors (Fig. 5B ). The data raise the possibility of a novel mode of interaction between dimeric HLA-G complexes and LIR-1/2 or other immunomodulatory receptors.
Acknowledgments
We thank the staff at BioCars (Advanced Photon Source, Chicago) for assistance with data collection. J.R. was supported by a Wellcome Trust Senior Research Fellowship in Biomedical Science in Australia, and C.S.C. was supported by a Monash University Research Fellowship. This work was supported by the National Health and Medical Research Council, the Australian Research Council, and the Roche Organ Transplantation Research Foundation.
Footnotes
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↵ †† To whom correspondence may be addressed. E-mail: jamesm1{at}unimelb.edu.au or jamie.rossjohn{at}med.monash.edu.au.
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↵ ‡ C.S.C. and L.K.-N. contributed equally to this work.
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↵ ∥ J.R. and J.M. contributed equally to this work.
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Author contributions: L.K.-N., J.R., and J.M. designed research; C.S.C., L.K.-N., L.K., H.L.H., and J.R. performed research; E.M. and K.F. contributed new reagents/analytic tools; C.S.C., M.A.D., A.G.B., J.R., and J.M. analyzed data; and C.S.C., J.R., and J.M. wrote the paper.
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Abbreviations: β2M, β2-microglobulin; hc, heavy chain; LIR, leukocyte Ig-like receptor; MHC-I, MHC class I.
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Data deposition: The atomic coordinates and structure factors have been deposited in the Protein Data Bank, www.pdb.org (PDB ID code 1YDP).
- Copyright © 2005, The National Academy of Sciences
References
Crystal structure of HLA-G: A nonclassical MHC class I molecule expressed at the fetal–maternal interface
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