3ALQ

Crystal structure of TNF-TNFR2 complex

Summary for 3ALQ

• Entry DOI: 10.2210/pdb3alq/pdb
• Related: 1tnf 1tnr 2e7a 2zjc 2zpx
• Descriptor: Tumor necrosis factor, Tumor necrosis factor receptor superfamily member 1B, COBALT (II) ION, ... (4 entities in total)
• Functional Keywords: ligand-receptor complex, cytokine, cytokine-cytokine receptor complex, cytokine/cytokine receptor
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane; Single-pass type II membrane protein. Tumor necrosis factor, soluble form: Secreted: P01375; Isoform 1: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted. Tumor necrosis factor-binding protein 2: Secreted: P20333
• Total number of polymer chains: 12
• Total formula weight: 216741.20

Authors

Mukai, Y.,Nakamura, T.,Yamagata, Y.,Tsutsumi, Y. (deposition date: 2010-08-06, release date: 2010-11-17, Last modification date: 2024-11-20)

Primary citation

Mukai, Y.,Nakamura, T.,Yoshikawa, M.,Yoshioka, Y.,Tsunoda, S.I.,Nakagawa, S.,Yamagata, Y.,Tsutsumi, Y.
Solution of the Structure of the TNF-TNFR2 Complex
Sci.Signal., 3:ra83-ra83, 2010

PubMed Abstract: Tumor necrosis factor (TNF) is an inflammatory cytokine that has important roles in various immune responses, which are mediated through its two receptors, TNF receptor 1 (TNFR1) and TNFR2. Antibody-based therapy against TNF is used clinically to treat several chronic autoimmune diseases; however, such treatment sometimes results in serious side effects, which are thought to be caused by the blocking of signals from both TNFRs. Therefore, knowledge of the structural basis for the recognition of TNF by each receptor would be invaluable in designing TNFR-selective drugs. Here, we solved the 3.0 angstrom resolution structure of the TNF-TNFR2 complex, which provided insight into the molecular recognition of TNF by TNFR2. Comparison to the known TNFR1 structure highlighted several differences between the ligand-binding interfaces of the two receptors. Additionally, we also demonstrated that TNF-TNFR2 formed aggregates on the surface of cells, which may be required for signal initiation. These results may contribute to the design of therapeutics for autoimmune diseases.

PubMed: 21081755
DOI: 10.1126/scisignal.2000954

Experimental method

X-RAY DIFFRACTION (3 Å)