A native IgE in complex with profilin provides insights into allergen recognition and cross-reactivity

García-Ramírez, Benjamín; Mares-Mejía, Israel; Rodríguez-Hernández, Annia; Cano-Sánchez, Patricia; Torres-Larios, Alfredo; Ortega, Enrique; Rodríguez-Romero, Adela

doi:10.1038/s42003-022-03718-w

A native IgE in complex with profilin provides insights into allergen recognition and cross-reactivity

Journal Article · Wed Jul 27 00:00:00 EDT 2022 · Communications Biology

DOI:https://doi.org/10.1038/s42003-022-03718-w· OSTI ID:1982175

^[1]; ^[1]; Rodríguez-Hernández, Annia ^[1]; Cano-Sánchez, Patricia ^[1]; ^[1]; Ortega, Enrique ^[1]; ^[1]

Univ. Nacional Autonoma de Mexico (UNAM), Mexico City (Mexico)

Allergies have become a rising health problem, where plentiful substances can trigger IgE-mediated allergies in humans. While profilins are considered minor allergens, these ubiquitous proteins are primary molecules involved in cross-reactivity and pollen-food allergy syndrome. Here we report the first crystal structures of murine Fab/IgE, with its chains naturally paired, in complex with the allergen profilin from Hevea brasiliensis (Hev b 8). The crystallographic models revealed that the IgE’s six complementarity-determining regions (CDRs) interact with the allergen, comprising a rigid paratope-epitope surface of 926 Å², which includes an extensive network of interactions. Interestingly, we also observed previously unreported flexibility at Fab/IgE’s elbow angle, which did not influence the shape of the paratope. The Fab/IgE exhibits a high affinity for Hev b 8, even when using 1 M NaCl in BLI experiments. Finally, based on the encouraging cross-reactivity assays using two mutants of the maize profilin (Zea m 12), this antibody could be a promising tool in IgE engineering for diagnosis and research applications.

View Accepted Manuscript (DOE)

Research Organization:: Brookhaven National Laboratory (BNL), Upton, NY (United States). National Synchrotron Light Source II (NSLS-II)

Sponsoring Organization:: Conacyt, Mexico City; National Institute of General Medical Sciences (NIGMS); National Institutes of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER); Universidad Nacional Autónoma de México (UNAM) (DGAPA)

Grant/Contract Number:: SC0012704

OSTI ID:: 1982175

Journal Information:: Communications Biology, Journal Name: Communications Biology Journal Issue: 1 Vol. 5; ISSN 2399-3642

Publisher:: Springer NatureCopyright Statement

Country of Publication:: United States

Language:: English

References (49)

UCSF Chimera?A visualization system for exploratory research and analysis Pettersen, Eric F.; Goddard, Thomas D.; Huang, Conrad C. Journal of Computational Chemistry, Vol. 25, Issue 13 https://doi.org/10.1002/jcc.20084	journal	January 2004
The role of FcεRI expressed in dendritic cells and monocytes Shin, Jeoung-Sook; Greer, Alexandra M. Cellular and Molecular Life Sciences, Vol. 72, Issue 12 https://doi.org/10.1007/s00018-015-1870-x	journal	February 2015
Proteolytic digestion of mouse IgE Haba, Seiji; Nisonoff, Alfred Journal of Immunological Methods, Vol. 138, Issue 1 https://doi.org/10.1016/0022-1759(91)90059-O	journal	April 1991
Elbow Flexibility and Ligand-Induced Domain Rearrangements in Antibody Fab NC6.8: Large Effects of a Small Hapten Sotriffer, Christoph A.; Rode, Bernd M.; Varga, Janos M. Biophysical Journal, Vol. 79, Issue 2 https://doi.org/10.1016/S0006-3495(00)76320-X	journal	August 2000
Comparative binding of soluble fragments (derCD23, sCD23, and exCD23) of recombinant human CD23 to CD21 (SCR 1-2) and native IgE, and their effect on IgE regulation Bowles, Sandra Lyn; Jaeger, Christiane; Ferrara, Claudia Cellular Immunology, Vol. 271, Issue 2 https://doi.org/10.1016/j.cellimm.2011.08.003	journal	January 2011
An Alternative Binding Mode of IGHV3-53 Antibodies to the SARS-CoV-2 Receptor Binding Domain Wu, Nicholas C.; Yuan, Meng; Liu, Hejun Cell Reports, Vol. 33, Issue 3 https://doi.org/10.1016/j.celrep.2020.108274	journal	October 2020
An experimental and modeling-based approach to locate IgE epitopes of plant profilin allergens López-Torrejón, Gema; Díaz-Perales, Araceli; Rodríguez, Julia Journal of Allergy and Clinical Immunology, Vol. 119, Issue 6 https://doi.org/10.1016/j.jaci.2007.02.004	journal	June 2007
Antibody Elbow Angles are Influenced by their Light Chain Class Stanfield, Robyn L.; Zemla, Adam; Wilson, Ian A. Journal of Molecular Biology, Vol. 357, Issue 5 https://doi.org/10.1016/j.jmb.2006.01.023	journal	April 2006
Stability of allergens Pekar, Judith; Ret, Davide; Untersmayr, Eva Molecular Immunology, Vol. 100 https://doi.org/10.1016/j.molimm.2018.03.017	journal	August 2018
Novel murine mAbs define specific and cross-reactive epitopes on the latex profilin panallergen Hev b 8 Mares-Mejía, Israel; García-Ramírez, Benjamín; Torres-Larios, Alfredo Molecular Immunology, Vol. 128 https://doi.org/10.1016/j.molimm.2020.09.017	journal	December 2020
Molecular Interactions between a Recombinant IgE Antibody and the β-Lactoglobulin Allergen Niemi, Merja; Jylhä, Sirpa; Laukkanen, Marja-Leena Structure, Vol. 15, Issue 11 https://doi.org/10.1016/j.str.2007.09.012	journal	November 2007
Analysis and Control of Protein Crystallization Using Short Peptide Tags That Change Solubility without Affecting Structure, Thermal Stability, and Function Islam, Mohammad Monirul; Nakamura, Shigeyoshi; Noguchi, Keiichi Crystal Growth & Design, Vol. 15, Issue 6 https://doi.org/10.1021/acs.cgd.5b00010	journal	May 2015
Analysis of the Structural and Immunological Stability of 2S Albumin, Nonspecific Lipid Transfer Protein, and Profilin Allergens from Mustard Seeds Sirvent, Sofía; Palomares, Oscar; Cuesta-Herranz, Javier Journal of Agricultural and Food Chemistry, Vol. 60, Issue 23 https://doi.org/10.1021/jf300555h	journal	December 2011
New developments in FcεRI regulation, function and inhibition Kraft, Stefan; Kinet, Jean-Pierre Nature Reviews Immunology, Vol. 7, Issue 5 https://doi.org/10.1038/nri2072	journal	May 2007
Genomes of Asgard archaea encode profilins that regulate actin Akıl, Caner; Robinson, Robert C. Nature, Vol. 562, Issue 7727 https://doi.org/10.1038/s41586-018-0548-6	journal	October 2018
Structural insights into the IgE mediated responses induced by the allergens Hev b 8 and Zea m 12 in their dimeric forms Mares-Mejía, Israel; Martínez-Caballero, Siseth; Garay-Canales, Claudia Scientific Reports, Vol. 6, Issue 1 https://doi.org/10.1038/srep32552	journal	September 2016
The central role of FcεRI in allergy Von Bubnoff, D.; Novak, N.; Kraft, S. Clinical and Experimental Dermatology, Vol. 28, Issue 2 https://doi.org/10.1046/j.1365-2230.2003.01209.x	journal	March 2003
Allergic reactions to drugs: Implications for perioperative care Golembiewski, Julie A. Journal of PeriAnesthesia Nursing, Vol. 17, Issue 6 https://doi.org/10.1053/jpan.2002.36669	journal	December 2002
Occupational Asthma Tarlo, Susan M.; Lemiere, Catherine New England Journal of Medicine, Vol. 370, Issue 7 https://doi.org/10.1056/NEJMra1301758	journal	February 2014
Accurate secondary structure prediction and fold recognition for circular dichroism spectroscopy Micsonai, András; Wien, Frank; Kernya, Linda Proceedings of the National Academy of Sciences, Vol. 112, Issue 24 https://doi.org/10.1073/pnas.1500851112	journal	June 2015
Structure of a patient-derived antibody in complex with allergen reveals simultaneous conventional and superantigen-like recognition Mitropoulou, Alkistis N.; Bowen, Holly; Dodev, Tihomir S. Proceedings of the National Academy of Sciences, Vol. 115, Issue 37 https://doi.org/10.1073/pnas.1806840115	journal	August 2018
A Fluorescent Biosensor Reveals Conformational Changes in Human Immunoglobulin E Fc: IMPLICATIONS FOR MECHANISMS OF RECEPTOR BINDING, INHIBITION, AND ALLERGEN RECOGNITION Hunt, James; Keeble, Anthony H.; Dale, Robert E. Journal of Biological Chemistry, Vol. 287, Issue 21 https://doi.org/10.1074/jbc.M111.331967	journal	March 2012
Structural, Functional, and Immunological Characterization of Profilin Panallergens Amb a 8, Art v 4, and Bet v 2 Offermann, Lesa R.; Schlachter, Caleb R.; Perdue, Makenzie L. Journal of Biological Chemistry, Vol. 291, Issue 30 https://doi.org/10.1074/jbc.M116.733659	journal	July 2016
A single glycan on IgE is indispensable for initiation of anaphylaxis Shade, Kai-Ting C.; Platzer, Barbara; Washburn, Nathaniel Journal of Experimental Medicine, Vol. 212, Issue 4 https://doi.org/10.1084/jem.20142182	journal	March 2015
Profilin Binding to Poly-l-Proline and Actin Monomers along with Ability to Catalyze Actin Nucleotide Exchange Is Required for Viability of Fission Yeast Lu, Jia; Pollard, Thomas D. Molecular Biology of the Cell, Vol. 12, Issue 4 https://doi.org/10.1091/mbc.12.4.1161	journal	April 2001
PRALINE: a multiple sequence alignment toolbox that integrates homology-extended and secondary structure information Simossis, V. A.; Heringa, J. Nucleic Acids Research, Vol. 33, Issue Web Server https://doi.org/10.1093/nar/gki390	journal	July 2005
PIC: Protein Interactions Calculator Tina, K. G.; Bhadra, R.; Srinivasan, N. Nucleic Acids Research, Vol. 35, Issue Web Server https://doi.org/10.1093/nar/gkm423	journal	May 2007
PDBsum new things Laskowski, R. A. Nucleic Acids Research, Vol. 37, Issue Database https://doi.org/10.1093/nar/gkn860	journal	January 2009
BeStSel: a web server for accurate protein secondary structure prediction and fold recognition from the circular dichroism spectra Micsonai, András; Wien, Frank; Bulyáki, Éva Nucleic Acids Research, Vol. 46, Issue W1 https://doi.org/10.1093/nar/gky497	journal	June 2018
Why Are Some Proteins Allergens? Huby, R. D. J. Toxicological Sciences, Vol. 55, Issue 2 https://doi.org/10.1093/toxsci/55.2.235	journal	June 2000
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/S0021889807021206	journal	July 2007
HKL -3000: the integration of data reduction and structure solution – from diffraction images to an initial model in minutes Minor, Wladek; Cymborowski, Marcin; Otwinowski, Zbyszek Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 8 https://doi.org/10.1107/S0907444906019949	journal	July 2006
XDS Kabsch, Wolfgang Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2 https://doi.org/10.1107/S0907444909047337	journal	January 2010
Integration, scaling, space-group assignment and post-refinement Kabsch, Wolfgang Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 133-144 https://doi.org/10.1107/S0907444909047374	journal	January 2010
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
Towards automated crystallographic structure refinement with phenix.refine Afonine, Pavel V.; Grosse-Kunstleve, Ralf W.; Echols, Nathaniel Acta Crystallographica Section D Biological Crystallography, Vol. 68, Issue 4 https://doi.org/10.1107/S0907444912001308	journal	March 2012
How good are my data and what is the resolution? Evans, Philip R.; Murshudov, Garib N. Acta Crystallographica Section D Biological Crystallography, Vol. 69, Issue 7 https://doi.org/10.1107/S0907444913000061	journal	June 2013
Structural analysis of glycoproteins: building N-linked glycans with Coot Emsley, Paul; Crispin, Max Acta Crystallographica Section D Structural Biology, Vol. 74, Issue 4 https://doi.org/10.1107/S2059798318005119	journal	April 2018
Structure of intact IgE and the mechanism of ligelizumab revealed by electron microscopy Jensen, Rasmus K.; Jabs, Frederic; Miehe, Michaela Allergy, Vol. 75, Issue 8 https://doi.org/10.1111/all.14222	journal	March 2020
Newly defined allergens in the WHO/IUIS Allergen Nomenclature Database during 01/2019‐03/2021 Sudharson, Srinidhi; Kalic, Tanja; Hafner, Christine Allergy, Vol. 76, Issue 11 https://doi.org/10.1111/all.15021	journal	August 2021
Structure and dynamics of IgE-receptor interactions: FcεRI and CD23/FcεRII Sutton, Brian J.; Davies, Anna M. Immunological Reviews, Vol. 268, Issue 1 https://doi.org/10.1111/imr.12340	journal	October 2015
Characterization of IgE epitopes of Cuc m 2, the major melon allergen, and their role in cross-reactivity with pollen profilins: B epitopes of melon profiling Tordesillas, L.; Pacios, L. F.; Palacín, A. Clinical & Experimental Allergy, Vol. 40, Issue 1 https://doi.org/10.1111/j.1365-2222.2009.03401.x	journal	December 2009
Hev b 8, the Hevea brasiliensis Latex Profilin, Is a Cross-Reactive Allergen of Latex, Plant Foods and Pollen Ganglberger, Erika; Radauer, Christian; Wagner, Stefan International Archives of Allergy and Immunology, Vol. 125, Issue 3 https://doi.org/10.1159/000053819	journal	January 2001
Profilins: Mimickers of Allergy or Relevant Allergens? Santos, Alexandra; Van Ree, Ronald International Archives of Allergy and Immunology, Vol. 155, Issue 3 https://doi.org/10.1159/000321178	journal	January 2011
Panallergens and their impact on the allergic patient Hauser, Michael; Roulias, Anargyros; Ferreira, Fátima Allergy, Asthma & Clinical Immunology, Vol. 6, Issue 1 https://doi.org/10.1186/1710-1492-6-1	journal	January 2010
Biolayer interferometry for DNA-protein interactions Barrows, John K.; Van Dyke, Michael W. PLOS ONE, Vol. 17, Issue 2 https://doi.org/10.1371/journal.pone.0263322	journal	February 2022
High-Affinity IgE Recognition of a Conformational Epitope of the Major Respiratory Allergen Phl p 2 As Revealed by X-Ray Crystallography Padavattan, Sivaraman; Flicker, Sabine; Schirmer, Tilman The Journal of Immunology, Vol. 182, Issue 4 https://doi.org/10.4049/jimmunol.0803018	journal	February 2009
Comparisons of the Ability of Human IgG3 Hinge Mutants, IgM, IgE, and IgA2, to Form Small Immune Complexes: A Role for Flexibility and Geometry Roux, Kenneth H.; Strelets, Lioudmila; Brekke, Ole Henrik The Journal of Immunology, Vol. 161, Issue 8 https://doi.org/10.4049/jimmunol.161.8.4083	journal	October 1998
Cross-reactivity between aeroallergens and food allergens Popescu, Florin-Dan World Journal of Methodology, Vol. 5, Issue 2 https://doi.org/10.5662/wjm.v5.i2.31	journal	January 2015

Similar Records

Comparative structural and thermal stability studies of Cuc m 2.0101, Art v 4.0101 and other allergenic profilins

Journal Article · Wed Jul 17 20:00:00 EDT 2019 · Molecular Immunology · OSTI ID:1557311

Structural analysis of the endogenous glycoallergen Hev b 2 (endo-β-1,3-glucanase) from Hevea brasiliensis and its recognition by human basophils

Journal Article · Fri Jan 31 23:00:00 EST 2014 · Acta Crystallographica. Section D: Biological Crystallography · OSTI ID:22351309

Immunotherapy-induced neutralizing antibodies disrupt allergen binding and sustain allergen tolerance in peanut allergy

Journal Article · Mon Jan 16 19:00:00 EST 2023 · Journal of Clinical Investigation · OSTI ID:2423466

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Biophysical chemistry
Life Sciences & Biomedicine - Other Topics
Science & Technology - Other Topics
X-ray crystallography

A native IgE in complex with profilin provides insights into allergen recognition and cross-reactivity

Citation Formats

References (49)

Similar Records

Related Subjects