Zinc Induces Dimerization of the Class II Major Histocompatibility Complex Molecule That Leads to Cooperative Binding to a Superantigen

Li, Hongmin; Zhao, Yiwei; Guo, Yi; Zhong, Li; Eisele, Leslie E.; Mourad, Walid

doi:10.1074/jbc.m608482200

Cited by 18 publications

(17 citation statements)

References 65 publications

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“…These residues, like most involved in at the C1-C1 interface, are conserved across species (Figure S1), which implies a role for Zn 2+ in receptor multimerization. We note that Zn 2+ can induce dimerization of the class II major histocompatibility complex, leading to cooperative binding of a superantigen ligand (Li et al, 2007). Moreover, homophilic interactions of receptor Ig-type ectodomains play a central role in ligand-binding and cellular activation (Stuttfeld and Ballmer-Hofer, 2009; Xu and Jin, 2010; Yang et al, 2010).…”

Section: Resultsmentioning

confidence: 99%

Structural Basis for Ligand Recognition and Activation of RAGE

et al. 2010

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SUMMARY The receptor for advanced glycation end products (RAGE) is a pattern recognition receptor involved in inflammatory processes and is associated with diabetic complications, tumor outgrowth, and neurodegenerative disorders. RAGE induces cellular signaling events upon binding of a variety of ligands, such as glycated proteins, amyloid-β, HMGB1, and S100 proteins. The X-ray crystal structure of the VC1 ligand-binding region of the human RAGE ectodomain was determined at 1.85 Å resolution. The VC1 ligand-binding surface was mapped onto the structure from titrations with S100B monitored by heteronuclear NMR spectroscopy. These NMR chemical shift perturbations were used as input for restrained docking calculations to generate a model for the VC1-S100B complex. Together, the arrangement of VC1 molecules in the crystal and complementary biochemical studies suggest a role for self-association in RAGE function. Our results enhance understanding of the functional outcomes of S100 protein binding to RAGE and provide insight into mechanistic models for how the receptor is activated.

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Section: Resultsmentioning

confidence: 99%

Structural Basis for Ligand Recognition and Activation of RAGE

et al. 2010

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“…The involvement of zinc in superantigen activation of T cells has been well established [5]. A zinc-binding site was revealed close to the MHC-binding site on superantigen staphylococcal enterotoxin A (SEA) and several other superantigens [6, 7]. This site interacts with the MHCII molecule via the exposed β His81 of the β 1 domain.…”

Section: Metal and Immune Systemsmentioning

confidence: 99%

Structural basis of metal hypersensitivity

Wang

Dai

2012

Immunol Res

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Metal hypersensitivity is a common immune disorder. Human immune systems mount the allergic attacks on metal ions through skin contacts, lung inhalation and metal-containing artificial body implants. The consequences can be simple annoyances to life-threatening systemic illness. Allergic hyper-reactivities to nickel (Ni) and beryllium (Be) are the best-studied human metal hypersensitivities. Ni-contact dermatitis affects 10 % of the human population, whereas Be compounds are the culprits of chronic Be disease (CBD). αβ T cells (T cells) play a crucial role in these hypersensitivity reactions. Metal ions work as haptens and bind to the surface of major histocompatibility complex (MHC) and peptide complex. This modifies the binding surface of MHC and triggers the immune response of T cells. Metal-specific αβ T cell receptors (TCRs) are usually MHC restricted, especially MHC class II (MHCII) restricted. Numerous models have been proposed, yet the mechanisms and molecular basis of metal hypersensitivity remain elusive. Recently, we determined the crystal structures of the Ni and Be presenting human MHCII molecules, HLA-DR52c (DRA*0101, DRB3*0301) and HLA-DP2 (DPA1*0103, DPB1*0201). These structures revealed unusual features of MHCII molecules and shed light on how metal ions are recognized by T cells.

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“…A crucial role in MHC-II, EPO, MT, and GS production seems to be played by zinc, a transition metal that is capable of stimulating EPO and MT production [87][88][89][90]. Furthermore, zinc ions have been shown to induce the dimerization of class II MHC molecules, increasing their activity [88][89][90][91].…”

Section: Discussionmentioning

confidence: 99%

Impaired Synthesis of Erythropoietin, Glutamine Synthetase and Metallothionein in the Skin of NOD/SCID/γ c null and Foxn1 nu/nu Mice with Misbalanced Production of MHC Class II Complex

et al. 2009

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Most skin pathologies are characterized by unbalanced synthesis of major histocompatability complex II (MHC-II) proteins. Healthy skin keratinocytes simultaneously produce large amounts of MHC-II and regeneration-supporting proteins, e.g. erythropoietin (EPO), EPO receptor (EPOR), glutamine synthetase (GS) and metallothionein (MT). To investigate the level of regeneration-supporting proteins in the skin during misbalanced production of MHC-II, skin sections from nonobese diabetic/severe combined immunodeficient (NOD/SCID)/gamma (c) (null) and or Foxn1 nu/nu mice which are a priory known to under- and over-express MHC II, respectively, were used. Double immunofluorescence analysis of NOD/SCID/gamma (c) (null) skin sections showed striking decrease in expression of MHC-II, EPO, GS and MT. In Foxn1 nu/nu mouse skin, GS was strongly expressed in epidermis and in hair follicles (HF), which lacked EPO. In nude mouse skin EPO and MHC-II were over-expressed in dermal fibroblasts and they were completely absent from cortex, channel, medulla and keratinocytes surrounding the HF, suggest a role for EPO in health and pathology of hair follicle. The level of expression of EPO and GS in both mutant mice was confirmed by results of Western blot analyses. Strong immunoresponsiveness of EPOR in the hair channels of NOD/SCID/gamma (c) (null) mouse skin suggests increased requirements of skin cells for EPO and possible benefits of exogenous EPO application during disorders of immune system accompanied by loss MHC-II in skin cells.

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Zinc Induces Dimerization of the Class II Major Histocompatibility Complex Molecule That Leads to Cooperative Binding to a Superantigen

Cited by 18 publications

References 65 publications

Structural Basis for Ligand Recognition and Activation of RAGE

Structural Basis for Ligand Recognition and Activation of RAGE

Structural basis of metal hypersensitivity

Impaired Synthesis of Erythropoietin, Glutamine Synthetase and Metallothionein in the Skin of NOD/SCID/γ c null and Foxn1 nu/nu Mice with Misbalanced Production of MHC Class II Complex

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