ArticleProceedings of the National Academy of Sciences of the United States of America2013
Dimerization of LTβR by LTα1β2 is necessary and sufficient for signal transduction.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
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- TNFSF14-Derived Molecules as a Novel Treatment for Obesity and Type 2 Diabetes.International journal of molecular sciences · 2021Article
- Membrane lymphotoxin-αCell death & disease · 2021Article
- Clathrin- and dynamin-dependent endocytosis limits canonical NF-κB signaling triggered by lymphotoxin β receptor.Cell communication and signaling : CCS · 2020Article
- Structural Basis of CD160:HVEM Recognition.Structure (London, England : 1993) · 2019Article
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- Structure of the 4-1BB/4-1BBL complex and distinct binding and functional properties of utomilumab and urelumab.Nature communications · 2018Article
- Repetitive ischemic injuries to the kidneys result in lymph node fibrosis and impaired healing.JCI insight · 2018Article
- Salivary factor LTRIN from Aedes aegypti facilitates the transmission of Zika virus by interfering with the lymphotoxin-β receptor.Nature immunology · 2018Article
- Binding Studies of TNF Receptor Superfamily (TNFRSF) Receptors on Intact Cells.The Journal of biological chemistry · 2016Article
- Evaluating the Use of Antibody Variable Region (Fv) Charge as a Risk Assessment Tool for Predicting Typical Cynomolgus Monkey Pharmacokinetics.The Journal of biological chemistry · 2015Article
- Principles of antibody-mediated TNF receptor activation.Cell death and differentiation · 2015Review
- Correlating RANK ligand/RANK binding kinetics with osteoclast formation and function.Journal of cellular biochemistry · 2015Article
- Immune Response in Hepatitis B Virus Infection.Cold Spring Harbor perspectives in medicine · 2015Review
Corrections and comments
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Authors and funding
6 authors at 1 institution.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Homotrimeric TNF superfamily ligands signal by inducing trimers of their cognate receptors. As a biologically active heterotrimer, Lymphotoxin(LT)α1β2 is unique in the TNF superfamily. How the three unique potential receptor-binding interfaces in LTα1β2 trigger signaling via LTβ Receptor (LTβR) resulting in lymphoid organogenesis and propagation of inflammatory signals is poorly understood. Here we show that LTα1β2 possesses two binding sites for LTβR with distinct affinities and that dimerization of LTβR by LTα1β2 is necessary and sufficient for signal transduction. The crystal structure of a complex formed by LTα1β2, LTβR, and the fab fragment of an antibody that blocks LTβR activation reveals the lower affinity receptor-binding site. Mutations targeting each potential receptor-binding site in an engineered single-chain variant of LTα1β2 reveal the high-affinity site. NF-κB reporter assays further validate that disruption of receptor interactions at either site is sufficient to prevent signaling via LTβR.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.