2erj

From Proteopedia

Crystal structure of the heterotrimeric interleukin-2 receptor in complex with interleukin-2

Overview

IL-2 is a cytokine that functions as a growth factor and central regulator, in the immune system and mediates its effects through ligand-induced, hetero-trimerization of the receptor subunits IL-2R alpha, IL-2R beta, and, gamma(c). Here, we describe the crystal structure of the trimeric assembly, of the human IL-2 receptor ectodomains in complex with IL-2 at 3.0 A, resolution. The quaternary structure is consistent with a stepwise, assembly from IL-2/IL-2R alpha to IL-2/IL-2R alpha/IL-2R beta to, IL-2/IL-2R alpha/IL-2R beta/gamma(c). The IL-2R alpha subunit forms the, largest of the three IL-2/IL-2R interfaces, which, together with the high, abundance of charge-charge interactions, correlates well with the rapid, association rate and high-affinity interaction of IL-2R alpha with IL-2 at, the cell surface. Surprisingly, IL-2R alpha makes no contacts with IL-2R, beta or gamma(c), and only minor changes are observed in the IL-2, structure in response to receptor binding. These findings support the, principal role of IL-2R alpha to deliver IL-2 to the signaling complex and, act as regulator of signal transduction. Cooperativity in assembly of the, final quaternary complex is easily explained by the extraordinarily, extensive set of interfaces found within the fully assembled IL-2, signaling complex, which nearly span the entire length of the IL-2R beta, and gamma(c) subunits. Helix A of IL-2 wedges tightly between IL-2R beta, and gamma(c) to form a three-way junction that coalesces into a composite, binding site for the final gamma(c) recruitment. The IL-2/gamma(c), interface itself exhibits the smallest buried surface and the fewest, hydrogen bonds in the complex, which is consistent with its promiscuous, use in other cytokine receptor complexes.

Disease

Known diseases associated with this structure: Combined immunodeficiency, X-linked, moderate OMIM:[308380], Diabetes mellitus, insulin-dependent, susceptibility to OMIM:[147730], Interleukin-2 receptor, alpha chain, deficiency of OMIM:[147730], Severe combined immunodeficiency due to IL2 deficiency OMIM:[147680], Severe combined immunodeficiency, X-linked OMIM:[308380]

About this Structure

2ERJ is a Protein complex structure of sequences from Homo sapiens with NAG as ligand. Full crystallographic information is available from OCA.

Reference

Crystal structure of the IL-2 signaling complex: paradigm for a heterotrimeric cytokine receptor., Stauber DJ, Debler EW, Horton PA, Smith KA, Wilson IA, Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2788-93. Epub 2006 Feb 13. PMID:16477002

Page seeded by OCA on Mon Nov 12 21:54:35 2007