From Proteopedia

proteopedia linkproteopedia link

spinqualitylabelsall models 2psm, resolution 2.19Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structure of Interleukin 15 in complex with Interleukin 15 receptor alpha

Overview

Interleukin (IL)-15 is a pleiotropic cytokine that plays a pivotal role in, both innate and adaptive immunity. IL-15 is unique among cytokines due to, its participation in a trans signaling mechanism in which IL-15Ralpha from, one subset of cells presents IL-15 to neighboring IL-2Rbeta/gamma(c), expressing cells. Here we present the crystal structure of IL-15 in, complex with the sushi domain of IL-15Ralpha. The structure reveals that, the alpha receptor-binding epitope of IL-15 adopts a unique conformation, which together with amino acid substitutions, permit specific interactions, with IL-15Ralpha that account for the exceptionally high affinity of the, IL-15*IL-15Ralpha complex. Interestingly, analysis of the topology of, IL-15 and IL-15Ralpha at the IL-15*IL-15Ralpha interface suggest that, IL-15 should be capable of participating in a cis signaling mechanism, similar to that of the related cytokine IL-2. Indeed, we present, biochemical data demonstrating that IL-15 is capable of efficiently, signaling in cis through IL-15Ralpha and IL-2Rbeta/gamma(c) expressed on, the surface of a single cell. Based on our data we propose that cis, presentation of IL-15 may be important in certain biological contexts, and, that flexibility of IL-15Ralpha permits IL-15 and its three receptor, components to be assembled identically at the ligand-receptor interface, whether IL-15 is presented in cis or trans. Finally, we have gained, insights into IL-15*IL-15Ralpha*IL-2Rbeta/gamma(c) quaternary complex, assembly through the use of molecular modeling.

About this Structure

2PSM is a Protein complex structure of sequences from Mus musculus with as ligand. Full crystallographic information is available from OCA.

Reference

Crystal structure of the Interleukin-15 Interleukin-15 Receptor alpha complex: Insights into trans and cis presentation., Olsen SK, Ota N, Kishishita S, Kukimoto-Niino M, Murayama K, Uchiyama H, Toyama M, Terada T, Shirouzu M, Kanagawa O, Yokoyama S, J Biol Chem. 2007 Oct 18;. PMID:17947230

Page seeded by OCA on Wed Jan 23 11:18:32 2008