3LB6

The structure of IL-13 in complex with IL-13Ralpha2

Summary for 3LB6

• Entry DOI: 10.2210/pdb3lb6/pdb
• Descriptor: Interleukin-13, Interleukin-13 receptor subunit alpha-2, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: cytokine, receptor, decoy, decoy receptor, glycoprotein, secreted, signaling protein-signaling protein complex, signaling protein/signaling protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 117723.84

Authors

Lupardus, P.J.,Garcia, K.C.,Birnbaum, M.E. (deposition date: 2010-01-07, release date: 2010-03-16, Last modification date: 2024-04-03)

Primary citation

Lupardus, P.J.,Birnbaum, M.E.,Garcia, K.C.
Molecular basis for shared cytokine recognition revealed in the structure of an unusually high affinity complex between IL-13 and IL-13Ralpha2.
Structure, 18:332-342, 2010

PubMed Abstract: Interleukin-13 is a cytokine important for development of T helper cell type 2 (Th2) responses and plays a critical role in asthma and allergy. The IL-13 Receptor alpha2 (IL-13Ralpha2) is a receptor for IL-13 lacking canonical Jak/STAT signaling functions. Here we present the crystal structure along with a mutational and biophysical analysis of the IL-13/IL-13Ralpha2 complex. While retaining a similar mode of IL-13 binding to its related signaling receptor, IL-13Ralpha1, IL-13Ralpha2 uses peripheral receptor residues unused in the IL-13/IL-13Ralpha1 complex to generate a larger and more complementary interface for IL-13. This results in a four orders of magnitude increase in affinity, to the femtomolar level, compared to IL-13Ralpha1. Alanine scanning mutagenesis of the IL-13 interface reveals several common "hotspot" residues important for binding to both receptors, but also identifies a prominent IL-13Ralpha2-specific contact. These results provide a framework for development of receptor subtype-selective IL-13 antagonists and indicate a decoy function for IL-13Ralpha2.

PubMed: 20223216
DOI: 10.1016/j.str.2010.01.003

Experimental method

X-RAY DIFFRACTION (3.05 Å)