The structure of the trimer of human 4-1BB ligand is unique among members of the tumor necrosis factor superfamily

Eun Young Won, Kiweon Cha, Jung Sue Byun, Dong Uk Kim, Sumi Shin, Byungchan Ahn, Young Ho Kim, Amanda J. Rice, Thomas Walz, Byoung S. Kwon, Hyun Soo Cho

Research output: Contribution to journalArticle

38 Citations (Scopus)

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-Å 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.

Original languageEnglish
Pages (from-to)9202-9210
Number of pages9
JournalJournal of Biological Chemistry
Volume285
Issue number12
DOIs
Publication statusPublished - 2010 Mar 19

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'The structure of the trimer of human 4-1BB ligand is unique among members of the tumor necrosis factor superfamily'. Together they form a unique fingerprint.

  • Cite this

    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. (2010). The structure of the trimer of human 4-1BB ligand is unique among members of the tumor necrosis factor superfamily. Journal of Biological Chemistry, 285(12), 9202-9210. https://doi.org/10.1074/jbc.M109.084442