ArticleProtein science : a publication of the Protein Society2018
Structural basis for tumor necrosis factor blockade with the therapeutic antibody golimumab.
Article in Protein science : a publication of the Protein Society, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- HDX-MS Detects Steric Protection and Trimeric Compaction of TNFα after It Binds Receptors or Antibodies.ACS omega · 2026Article
- Golimumab for the Treatment of Rheumatoid Arthritis: A Narrative Review of Pivotal Randomized Trials and Real-World Studies.Rheumatology and therapy · 2026Review
- Molecular determinants of TNFR1:TNFα binding and dynamics in a physiological membrane environment.Current research in structural biology · 2026Article
- Peptide Aptamer-Enabled Nanoplasmonic Digital Immunoassay for Ultrasensitive Cytokine Sensing in Early Inflammation and Immune Modulation.ACS sensors · 2026Article
- Rapid, Single-Step Monitoring of Monoclonal Antibody Bioavailability by Using a TNF-α-Based Multiepitope DNA Nanoswitch.Analytical chemistry · 2025Article
- Immunogenicity risk assessment for tailored mitigation and monitoring of biotherapeutics during development: recommendations from the European Immunogenicity Platform.Frontiers in immunology · 2025Review
- Membrane Protein Binding Interactions Studied in Live Cells via Diethylpyrocarbonate Covalent Labeling Mass Spectrometry.Analytical chemistry · 2023Article
- Physicochemical characterization and functionality comparison of Humira®(adalimumab), Remicade®(infliximab) and Simponi Aria®(golimumab).International journal of pharmaceutics · 2023Article
- Successful adalimumab graded challenge after allergic delayed reaction to golimumab in a woman with rheumatoid arthritis.Clinical case reports · 2023Article
- Complementary Structural Information for Antibody-Antigen Complexes from Hydrogen-Deuterium Exchange and Covalent Labeling Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2022Article
- Missense variants in the TNFA epitopes and their effects on interaction with therapeutic antibodies-in silico analysis.Journal, genetic engineering & biotechnology · 2022Article
- Identification, Efficacy, and Stability Evaluation of Succinimide Modification With a High Abundance in the Framework Region of Golimumab.Frontiers in chemistry · 2022Article
- Fisetin Attenuates Arsenic-Induced Hepatic Damage by Improving Biochemical, Inflammatory, Apoptotic, and Histological Profile: In Vivo and In Silico Approach.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Rational Design of Constrained Peptides as Protein Interface Inhibitors.Antibodies (Basel, Switzerland) · 2021Review
- Toward Overcoming Treatment Failure in Rheumatoid Arthritis.Frontiers in immunology · 2021Review
- Discovery of Marburg virus neutralizing antibodies from virus-naïve human antibody repertoires using large-scale structural predictions.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The trimer to monomer transition of Tumor Necrosis Factor-Alpha is a dynamic process that is significantly altered by therapeutic antibodies.Scientific reports · 2020Article
- Structural Basis for How Biologic Medicines Bind their Targets in Psoriasis Therapy.The Yale journal of biology and medicine · 2020Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor necrosis factor α (TNFα) is a proinflammatory cytokine, and elevated levels of TNFα in serum are associated with various autoimmune diseases, including rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn's disease (CD), psoriasis, and systemic lupus erythaematosus. TNFα performs its pleiotropic functions by binding to two structurally distinct transmembrane receptors, TNF receptor (TNFR) 1 and TNFR2. Antibody-based therapeutic strategies that block excessive TNFα signaling have been shown to be effective in suppressing such harmful inflammatory conditions. Golimumab (Simponi®) is an FDA-approved fully human monoclonal antibody targeting TNFα that has been widely used for the treatment of RA, AS, and CD. However, the structural basis underlying the inhibitory action of golimumab remains unclear. Here, we report the crystal structure of the Fv fragment of golimumab in complex with TNFα at a resolution of 2.73 Å. The resolved structure reveals that golimumab binds to a distinct epitope on TNFα that does not overlap with the binding residues of TNFR2. Golimumab exerts its inhibitory effect by preventing binding of TNFR1 and TNFR2 to TNFα by steric hindrance. Golimumab does not induce conformational changes in TNFα that could affect receptor binding. This mode of action is specific to golimumab among the four anti-TNFα therapeutic antibodies currently approved for clinical use.
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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.