2X29

Crystal structure of human4-1BB ligand ectodomain

Replaces:  2WAK

Summary for 2X29

• Entry DOI: 10.2210/pdb2x29/pdb
• Descriptor: TUMOR NECROSIS FACTOR LIGAND SUPERFAMILY MEMBER 9 (2 entities in total)
• Functional Keywords: signal-anchor, cytokine, cell adhesion
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Membrane; Single-pass type II membrane protein: P41273
• Total number of polymer chains: 1
• Total formula weight: 17818.93

Authors

Won, E.Y.,Cho, H.S. (deposition date: 2010-01-12, release date: 2010-03-23, Last modification date: 2024-11-13)

Primary citation

Won, E.Y.,Cha, K.,Byun, J.S.,Kim, D.U.,Shin, S.,Ahn, B.,Kim, Y.H.,Rice, A.J.,Walz, T.,Kwon, B.S.,Cho, H.S.
The Structure of the Trimer of Human 4-1Bb Ligand is Unique Among Members of the Tumor Necrosis Factor Superfamily.
J.Biol.Chem., 285:9202-, 2010

PubMed Abstract: 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.

PubMed: 20032458
DOI: 10.1074/JBC.M109.084442

Experimental method

X-RAY DIFFRACTION (2.3 Å)