Structural insights into the common γ-chain family of cytokines and receptors from the interleukin-7 pathway.

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TitleStructural insights into the common γ-chain family of cytokines and receptors from the interleukin-7 pathway.
Publication TypeJournal Article
Year of Publication2012
AuthorsWalsh, STR
JournalImmunol Rev
Volume250
Issue1
Pagination303-16
Date Published2012 Nov
ISSN1600-065X
KeywordsBinding Sites, Glycosylation, Humans, Interleukin-7, Kinetics, Models, Molecular, Protein Binding, Protein Conformation, Protein Multimerization, Receptors, Interleukin-7, Signal Transduction, Static Electricity, T-Lymphocytes, Thermodynamics
Abstract

Over the past 13 years, numerous crystal structures of complexes of the common γ-chain (γ(c)) cytokine receptors and their cytokines have been solved. Even with the remarkable progress in the structural biology of γ(c) receptors and their cytokines or interleukins, there are valuable lessons to be learned from the structural and biophysical studies of interleukin-7 (IL-7) and its α-receptor (IL-7Rα) and comparisons with other γ(c) family members. The structure of the IL-7/IL-7Rα complex teaches that interfaces between the γ(c) interleukins and their receptors can vary in size, polarity, and specificity, and that significant conformational changes might be necessary for complexes of interleukins and their receptors to bind the shared, activating γ(c) receptor. Binding, kinetic, and thermodynamic studies of IL-7 and IL-7Rα show that glycosylation and electrostatics can be important to interactions between interleukins and their receptor, even where the glycans and charged residues are distant from the interface. The structure of the IL-7Rα homodimer is a reminder that often-ignored non-activating complexes likely perform roles just as important to signaling as activating complexes. And last but not least, the structural and biophysical studies help explain and potentially treat the diseases caused by aberrant IL-7 signaling.

DOI10.1111/j.1600-065X.2012.01160.x
Alternate JournalImmunol. Rev.
PubMed ID23046137
PubMed Central IDPMC3471675
Grant ListAI72142 / AI / NIAID NIH HHS / United States
R01 AI072142 / AI / NIAID NIH HHS / United States