Document Detail

Structural insights into the common γ-chain family of cytokines and receptors from the interleukin-7 pathway.
MedLine Citation:
PMID:  23046137     Owner:  NLM     Status:  MEDLINE    
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.
Scott T R Walsh
Related Documents :
23719857 - Evolution and function of chemokine receptors in the immune system of lower vertebrates.
23104057 - Neuropilins lock secreted semaphorins onto plexins in a ternary signaling complex.
23992407 - Prenatal alcohol exposure is associated with altered subcellular distribution of glucoc...
23144627 - A targeted glycan-related gene screen reveals heparan sulfate proteoglycan sulfation re...
15258717 - The role of m1 muscarinic receptor agonism of n-desmethylclozapine in the unique clinic...
11050147 - Bradykinin, but not muscarinic, inhibition of m-current in rat sympathetic ganglion neu...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Immunological reviews     Volume:  250     ISSN:  1600-065X     ISO Abbreviation:  Immunol. Rev.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-10     Completed Date:  2013-02-25     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  7702118     Medline TA:  Immunol Rev     Country:  England    
Other Details:
Languages:  eng     Pagination:  303-16     Citation Subset:  IM    
Copyright Information:
© 2012 John Wiley & Sons A/S.
Department of Cell Biology and Molecular Genetics, Institute for Bioscience and Biotechnology Research, W. M. Keck Laboratory for Structural Biology, Rockville, MD, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Binding Sites
Interleukin-7 / chemistry*,  immunology,  metabolism
Models, Molecular
Protein Binding
Protein Conformation
Protein Multimerization
Receptors, Interleukin-7 / chemistry*,  immunology,  metabolism
Signal Transduction
Static Electricity
T-Lymphocytes / immunology*,  metabolism
Grant Support
Reg. No./Substance:
0/IL7 protein, human; 0/Interleukin-7; 0/Receptors, Interleukin-7

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  The GM-CSF/IL-3/IL-5 cytokine receptor family: from ligand recognition to initiation of signaling.
Next Document:  Structural and dynamic determinants of type I interferon receptor assembly and their functional inte...