|2x29, resolution 2.30Å ()|
CRYSTAL STRUCTURE OF HUMAN4-1BB LIGAND ECTODOMAIN
Binding of the 4-1BB ligand (4-1BBL) to its receptor, 4-1BB, provides the T lymphocyte with co-stimulatory signals for survival, proliferation, and differentiation. Importantly, the 4-1BB-4-1BBL pathway is a well known target for anti-cancer immunotherapy. Here we present the 2.3-A crystal structure of the extracellular domain of human 4-1BBL. The ectodomain forms a homotrimer with an extended, three-bladed propeller structure that differs from trimers formed by other members of the tumor necrosis factor (TNF) superfamily. Based on the 4-1BBL structure, we modeled its complex with 4-1BB, which was consistent with images obtained by electron microscopy, and verified the binding site by site-directed mutagenesis. This structural information will facilitate the development of immunotherapeutics targeting 4-1BB.
The structure of the trimer of human 4-1BB ligand is unique among members of the tumor necrosis factor superfamily., Won EY, Cha K, Byun JS, Kim DU, Shin S, Ahn B, Kim YH, Rice AJ, Walz T, Kwon BS, Cho HS, J Biol Chem. 2010 Mar 19;285(12):9202-10. Epub 2009 Dec 23. PMID:20032458
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
- Won EY, Cha K, Byun JS, Kim DU, Shin S, Ahn B, Kim YH, Rice AJ, Walz T, Kwon BS, Cho HS. The structure of the trimer of human 4-1BB ligand is unique among members of the tumor necrosis factor superfamily. J Biol Chem. 2010 Mar 19;285(12):9202-10. Epub 2009 Dec 23. PMID:20032458 doi:10.1074/jbc.M109.084442