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Structure analysis of the IL-5 ligand-receptor complex reveals a wrench-like architecture for IL-5Rα.

Patino E, Kotzsch A, Saremba S, Nickel J, Schmitz W, Sebald W, Mueller TD
Structure 19 1864-75 (2011)
Cited: 18 times
EuropePMC logo PMID: 22153509

Abstract

Interleukin-5 (IL-5) is the key mediator for the function of eosinophil granulocytes, whose deregulation is characteristic of hypereosinophilic diseases and presumably contributes to allergic asthma. IL-5 signaling involves two transmembrane receptors, IL-5Rα and the common β chain, which upon formation of the ternary complex activate the JAK/STAT signaling cascade. To investigate the mechanism underlying ligand-receptor recognition, we determined the structure of IL-5 bound to the extracellular domain of IL-5Rα. IL-5 makes contact with all three fibronectin III-like domains of IL-5Rα, with the receptor architecture resembling a wrench. Mutagenesis data provide evidence that this wrench-like architecture is likely preformed. The structure demonstrates that for steric reasons, homodimeric IL-5 can bind only one receptor molecule, even though two equivalent receptor-binding sites exist. In regard to strong efforts being made to develop IL-5 antagonists for treating asthma and hypereosinophilic diseases, the advances in molecular understanding provided by this structure are of greatest value.

Reviews - 3qt2 mentioned but not cited (1)

  1. Role of the β Common (βc) Family of Cytokines in Health and Disease. Hercus TR, Kan WLT, Broughton SE, Tvorogov D, Ramshaw HS, Sandow JJ, Nero TL, Dhagat U, Thompson EJ, Shing KSCT, McKenzie DR, Wilson NJ, Owczarek CM, Vairo G, Nash AD, Tergaonkar V, Hughes T, Ekert PG, Samuel MS, Bonder CS, Grimbaldeston MA, Parker MW, Lopez AF. Cold Spring Harb Perspect Biol 10 (2018)

Articles - 3qt2 mentioned but not cited (7)

  1. OGlcNAcylation and phosphorylation have opposing structural effects in tau: phosphothreonine induces particular conformational order. Brister MA, Pandey AK, Bielska AA, Zondlo NJ. J. Am. Chem. Soc. 136 3803-3816 (2014)
  2. Structural basis of interleukin-5 dimer recognition by its α receptor. Kusano S, Kukimoto-Niino M, Hino N, Ohsawa N, Ikutani M, Takaki S, Sakamoto K, Hara-Yokoyama M, Shirouzu M, Takatsu K, Yokoyama S. Protein Sci. 21 850-864 (2012)
  3. Crystallization and preliminary X-ray diffraction analysis of the interleukin-3 alpha receptor bound to the Fab fragment of antibody CSL362. Broughton SE, Hercus TR, Nero TL, Dhagat U, Owczarek CM, Hardy MP, Fabri LJ, Scotney PD, Nash AD, Wilson NJ, Lopez AF, Parker MW. Acta Crystallogr F Struct Biol Commun 70 358-361 (2014)
  4. A dual role for the N-terminal domain of the IL-3 receptor in cell signalling. Broughton SE, Hercus TR, Nero TL, Kan WL, Barry EF, Dottore M, Cheung Tung Shing KS, Morton CJ, Dhagat U, Hardy MP, Wilson NJ, Downton MT, Schieber C, Hughes TP, Lopez AF, Parker MW. Nat Commun 9 386 (2018)
  5. A New Investigation into the Molecular Mechanism of Andrographolide towards Reducing Cytokine Storm. Alzahrani A. Molecules 27 4555 (2022)
  6. Cytosporones with Anti-Inflammatory Activities from the Mangrove Endophytic Fungus Phomopsis sp. QYM-13. Wang G, Yuan Y, Li Z, Zhu J, She Z, Chen Y. Mar Drugs 21 631 (2023)
  7. Engineering of Humanized Antibodies Against Human Interleukin 5 Receptor Alpha Subunit That Cause Potent Antibody-Dependent Cell-Mediated Cytotoxicity. Kim JE, Lee DH, Jung K, Kim EJ, Choi Y, Park HS, Kim YS. Front Immunol 11 593748 (2020)


Reviews citing this publication (4)

  1. The GM-CSF/IL-3/IL-5 cytokine receptor family: from ligand recognition to initiation of signaling. Broughton SE, Dhagat U, Hercus TR, Nero TL, Grimbaldeston MA, Bonder CS, Lopez AF, Parker MW. Immunol. Rev. 250 277-302 (2012)
  2. Insights into cytokine-receptor interactions from cytokine engineering. Spangler JB, Moraga I, Mendoza JL, Garcia KC. Annu. Rev. Immunol. 33 139-167 (2015)
  3. Signalling by the βc family of cytokines. Hercus TR, Dhagat U, Kan WL, Broughton SE, Nero TL, Perugini M, Sandow JJ, D'Andrea RJ, Ekert PG, Hughes T, Parker MW, Lopez AF. Cytokine Growth Factor Rev. 24 189-201 (2013)
  4. The βc receptor family - Structural insights and their functional implications. Broughton SE, Nero TL, Dhagat U, Kan WL, Hercus TR, Tvorogov D, Lopez AF, Parker MW. Cytokine 74 247-258 (2015)

Articles citing this publication (6)

  1. Characterization of pathogenic human monoclonal autoantibodies against GM-CSF. Wang Y, Thomson CA, Allan LL, Jackson LM, Olson M, Hercus TR, Nero TL, Turner A, Parker MW, Lopez AL, Waddell TK, Anderson GP, Hamilton JA, Schrader JW. Proc. Natl. Acad. Sci. U.S.A. 110 7832-7837 (2013)
  2. Dual mechanism of interleukin-3 receptor blockade by an anti-cancer antibody. Broughton SE, Hercus TR, Hardy MP, McClure BJ, Nero TL, Dottore M, Huynh H, Braley H, Barry EF, Kan WL, Dhagat U, Scotney P, Hartman D, Busfield SJ, Owczarek CM, Nash AD, Wilson NJ, Parker MW, Lopez AF. Cell Rep 8 410-419 (2014)
  3. A Miniature Protein Stabilized by a Cation-π Interaction Network. Craven TW, Cho MK, Traaseth NJ, Bonneau R, Kirshenbaum K. J. Am. Chem. Soc. 138 1543-1550 (2016)
  4. A two-in-one antibody engineered from a humanized interleukin 4 antibody through mutation in heavy chain complementarity-determining regions. Lee CV, Koenig P, Fuh G. MAbs 6 622-627 (2014)
  5. Identification of a fourth ancient member of the IL-3/IL-5/GM-CSF cytokine family, KK34, in many mammals. Yamaguchi T, Schares S, Fischer U, Dijkstra JM. Dev. Comp. Immunol. 65 268-279 (2016)
  6. Development of an inhibiting antibody against equine interleukin 5 to treat insect bite hypersensitivity of horses. Langreder N, Schäckermann D, Meier D, Becker M, Schubert M, Dübel S, Reinard T, Figge-Wegener S, Roßbach K, Bäumer W, Ladel S, Hust M. Sci Rep 13 4029 (2023)


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