TY - JOUR
T1 - The structure of the trimer of human 4-1BB ligand is unique among members of the tumor necrosis factor superfamily
AU - Won, Eun Young
AU - Cha, Kiweon
AU - Byun, Jung Sue
AU - Kim, Dong Uk
AU - Shin, Sumi
AU - Ahn, Byungchan
AU - Kim, Young Ho
AU - Rice, Amanda J.
AU - Walz, Thomas
AU - Kwon, Byoung S.
AU - Cho, Hyun Soo
PY - 2010/3/19
Y1 - 2010/3/19
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M109.084442
DO - 10.1074/jbc.M109.084442
M3 - Article
C2 - 20032458
AN - SCOPUS:77950568379
SN - 0021-9258
VL - 285
SP - 9202
EP - 9210
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 12
ER -
