2PSM

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

Summary for 2PSM

• Entry DOI: 10.2210/pdb2psm/pdb
• Descriptor: Interleukin-15, Interleukin-15 receptor alpha chain, BENZAMIDINE, ... (4 entities in total)
• Functional Keywords: cytokine, glycoprotein, secreted, alternative splicing, endoplasmic reticulum, golgi apparatus, membrane, nucleus, phosphorylation, receptor, sushi, transmembrane, structural genomics, nppsfa, national project on protein structural and functional analyses, riken structural genomics/proteomics initiative, rsgi
• Biological source: Mus musculus (house mouse); More
• Cellular location: Secreted: P48346; Membrane; Single-pass type I membrane protein. Isoform 1: Endoplasmic reticulum membrane; Single-pass type I membrane protein. Isoform 3: Endoplasmic reticulum membrane; Single-pass type I membrane protein. Isoform 4: Endoplasmic reticulum membrane; Single-pass type I membrane protein. Isoform 6: Endoplasmic reticulum membrane; Single-pass type I membrane protein. Soluble interleukin-15 receptor subunit alpha: Secreted, extracellular space (By similarity): Q60819
• Total number of polymer chains: 4
• Total formula weight: 44439.90

Authors

Olsen, S.K.,Murayama, K.,Kishishita, S.,Kukimoto-Niino, M.,Terada, T.,Shirouzu, M.,Ota, N.,Kanagawa, O.,Yokoyama, S.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (deposition date: 2007-05-07, release date: 2007-11-06, Last modification date: 2024-10-16)

Primary citation

Olsen, S.K.,Ota, N.,Kishishita, S.,Kukimoto-Niino, M.,Murayama, K.,Uchiyama, H.,Toyama, M.,Terada, T.,Shirouzu, M.,Kanagawa, O.,Yokoyama, S.
Crystal Structure of the Interleukin-15{middle dot}Interleukin-15 Receptor {alpha} Complex: INSIGHTS INTO TRANS AND CIS PRESENTATION
J.Biol.Chem., 282:37191-37204, 2007

PubMed Abstract: 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-15 receptor alpha (IL-15Ralpha) from one subset of cells presents IL-15 to neighboring IL-2Rbeta/gammac-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, permits 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 suggests 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/gammac 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.gammac quaternary complex assembly through the use of molecular modeling.

PubMed: 17947230
DOI: 10.1074/jbc.M706150200

Experimental method

X-RAY DIFFRACTION (2.19 Å)