3bpl

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Template:STRUCTURE 3bpl

Crystal structure of the IL4-IL4R-Common Gamma ternary complex

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

Interleukin-4 and Interleukin-13 are cytokines critical to the development of T cell-mediated humoral immune responses, which are associated with allergy and asthma, and exert their actions through three different combinations of shared receptors. Here we present the crystal structures of the complete set of type I (IL-4Ralpha/gamma(c)/IL-4) and type II (IL-4Ralpha/IL-13Ralpha1/IL-4, IL-4Ralpha/IL-13Ralpha1/IL-13) ternary signaling complexes. The type I complex reveals a structural basis for gamma(c)'s ability to recognize six different gamma(c)-cytokines. The two type II complexes utilize an unusual top-mounted Ig-like domain on IL-13Ralpha1 for a novel mode of cytokine engagement that contributes to a reversal in the IL-4 versus IL-13 ternary complex assembly sequences, which are mediated through substantially different recognition chemistries. We also show that the type II receptor heterodimer signals with different potencies in response to IL-4 versus IL-13 and suggest that the extracellular cytokine-receptor interactions are modulating intracellular membrane-proximal signaling events.

Disease

Known disease associated with this structure: Combined immunodeficiency, X-linked, moderate OMIM:[308380], Severe combined immunodeficiency, X-linked OMIM:[308380]

About this Structure

3BPL is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Molecular and Structural Basis of Cytokine Receptor Pleiotropy in the Interleukin-4/13 System., Laporte SL, Juo ZS, Vaclavikova J, Colf LA, Qi X, Heller NM, Keegan AD, Garcia KC, Cell. 2008 Jan 25;132(2):259-272. PMID:18243101 Page seeded by OCA on Sun May 4 20:58:42 2008