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100 Years later: Celebrating the contributions of x-ray crystallography to allergy and clinical immunology  Anna Pomés, PhD, Maksymilian Chruszcz, PhD,

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Presentation on theme: "100 Years later: Celebrating the contributions of x-ray crystallography to allergy and clinical immunology  Anna Pomés, PhD, Maksymilian Chruszcz, PhD,"— Presentation transcript:

1 100 Years later: Celebrating the contributions of x-ray crystallography to allergy and clinical immunology  Anna Pomés, PhD, Maksymilian Chruszcz, PhD, Alla Gustchina, PhD, Wladek Minor, PhD, Geoffrey A. Mueller, PhD, Lars C. Pedersen, PhD, Alexander Wlodawer, PhD, Martin D. Chapman, PhD  Journal of Allergy and Clinical Immunology  Volume 136, Issue 1, Pages e10 (July 2015) DOI: /j.jaci Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 General outline of the process of structure determination by using x-ray crystallography. Crystals of horse Equ c 3 and Alt a 1 from Alternaria alternata grown by using the vapor diffusion technique and used for x-ray diffraction experiments are shown. The European Synchrotron Radiation Facility and Institute Laue-Langevin in Grenoble (France; 3, left; photographer: Christian Hendrich) is shown next to diffraction images obtained from a protein crystal used for structure determination (3N99; 3, right). Journal of Allergy and Clinical Immunology  , e10DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 X-ray crystal structures of human molecules involved in immunology and allergic disease. A, Complex of a human α/β T-cell receptor (TCR; orange and yellow), influenza HA antigen peptide (blue), and MHC class II molecule HLA-DR1 (green and fuchsia; 1FYT). B, Cytokine receptor IL-4 type I (blue and green) bound to cytokine IL-4 (fuchsia; 3BPL). C, IgE-Fc (Cε2, Cε3, and Cε4 domains; blue and fuchsia) bound to the extracellular domains of the high-affinity IgE receptor (FcεRI) α chain (yellow; 2Y7Q). D, Low-affinity IgE receptors (CD23, FcεRII; 4G9A). E, TLR4 (blue and fuchsia)–MD-2 (yellow)–LPS (green) complex (3FXI). Journal of Allergy and Clinical Immunology  , e10DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 X-ray crystal structures of selected allergens. A, Mus m 1 (1MUP). B, Bet v 1 (1BV1). C, Alt a 1 (3V0R). D, Bla g 1 (4JRB). E, Bla g 2 in complex with Fab of mAb 7C11 (2NR6; pink) superimposed with the mAb-Fab from the structure of Bla g 2 in complex with Fab of mAb 4C3 (3LIZ; green). F, Der p 1 in complex with 4C1 (pale yellow, 3RVW) superimposed with the mAb-Fab from the 2 structures of the allergen in complex with 10B9 (pale green; 4PP2) or 5H8 (pale orange, 4PP1). G, Bos d 5 in complex with the Fab of a recombinant IgE antibody. Allergens are shown in rainbow colors from the N-terminus (blue) to C-terminus (red) and ligands in magenta (Fig 3, A and D). Journal of Allergy and Clinical Immunology  , e10DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig E1 Structural alignment of Bla g 2 and Der p 2 with the respective homologous porcine pepsin and human MD-2. A, Bla g 2 (green) aligned to a structure of pepsin determined in 1990 at 1.80 Å. Aspartates 32 and 215 in the catalytic site of pepsin are at a closer distance than the equivalent aspartates in Bla g 2 (indicated in stick representation). B, Der p 2 (blue) aligned to MD-2. LPS bound to the MD-2 internal cavity is in fuchsia. Protein Data Bank accession codes are 3LIZ, 4PEP, 1KTJ, and 2E59, respectively. Pepsin and MD-2 are displayed in gray. Journal of Allergy and Clinical Immunology  , e10DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig E2 Exponential increase in the number of structures deposited to the Protein Data Bank (PDB) between 1976 and All the structures (red and blue) and the structures determined by using x-ray crystallography (red) are shown. Journal of Allergy and Clinical Immunology  , e10DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig E3 Resolution. Electron density maps calculated for x-ray crystal structures determined at higher resolution are much more detailed, allowing a more precise definition of the molecules under study. An example is provided by the maps calculated for 2 amino acids in 3 structures of Bla g 2 determined at lower (left) to higher (right) resolution. The corresponding structures are 2NR6, 3LIZ, and 1YG9. Journal of Allergy and Clinical Immunology  , e10DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 Fig E4 Allergen structures from mite and peanut allergens. A, Der p 2 (1KTJ). B, Der p 5 (3MQ1). C, Der p 7 (3H4Z). D, Ara h 1 (3S7I). E, Ara h 2 (3OB4). F, Ara h 5 (4ESP). Allergens are shown in rainbow colors from the N-terminus (blue) to C-terminus (red). Journal of Allergy and Clinical Immunology  , e10DOI: ( /j.jaci ) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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