ArticleProtein science : a publication of the Protein Society2017
Higher order structures of Adalimumab, Infliximab and their complexes with TNFα revealed by electron microscopy.
Article in Protein science : a publication of the Protein Society, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- HDX-MS Detects Steric Protection and Trimeric Compaction of TNFα after It Binds Receptors or Antibodies.ACS omega · 2026Article
- Immunosenescence in Older Patients with Psoriasis: Mechanistic Insights and Opportunities for Biologic Therapy.Psoriasis (Auckland, N.Z.) · 2026Review
- Psoriasis.Nature reviews. Disease primers · 2025Review
- Association of the TNFRSF1B-rs1061622 variant with nonresponse to infliximab in ulcerative colitis.Scientific reports · 2025Article
- Intestinal tissue levels of anti-TNF alpha, antibodies, and cytokines in paediatric Crohn disease.Scientific reports · 2025Article
- Cardiovascular Adverse Events Associated with Tumor Necrosis Factor-Alpha Inhibitors: A Real-World Pharmacovigilance Analysis.Journal of atherosclerosis and thrombosis · 2024Article
- Structure-based development of a canine TNF-α-specific antibody using adalimumab as a template.Protein science : a publication of the Protein Society · 2024Article
- Article
- Therapeutic TNF Inhibitors Exhibit Differential Levels of Efficacy in Accelerating Cutaneous Wound Healing.JID innovations : skin science from molecules to population health · 2024Article
- Physicochemical characterization and functionality comparison of Humira®(adalimumab), Remicade®(infliximab) and Simponi Aria®(golimumab).International journal of pharmaceutics · 2023Article
- The benefits of clustering in TNF receptor superfamily signaling.Frontiers in immunology · 2023Review
- HLAII peptide presentation of infliximab increases when complexed with TNF.Frontiers in immunology · 2022Article
- Early Feasibility Assessment: A Method for Accurately Predicting Biotherapeutic Dosing to Inform Early Drug Discovery Decisions.Frontiers in pharmacology · 2022Article
- Ozoralizumab, a Humanized Anti-TNFα NANOBODYFrontiers in immunology · 2022Article
- Infliximab Efficacy May Be Linked to Full TNF-α Blockade in Peripheral Compartment-A Double Central-Peripheral Target-Mediated Drug Disposition (TMDD) Model.Pharmaceutics · 2021Article
- Size-based characterization of adalimumab and TNF-α interactions using flow induced dispersion analysis: assessment of avidity-stabilized multiple bound species.Scientific reports · 2021Article
- Biochemical and structural characterization of a recombinant fibrinogen-related lectin from Penaeus monodon.Scientific reports · 2021Article
- Structural basis for tumor necrosis factor blockade with the therapeutic antibody golimumab.Protein science : a publication of the Protein Society · 2018Article
- Anti-adalimumab antibodies in a cohort of patients with juvenile idiopathic arthritis: incidence and clinical correlations.Clinical rheumatology · 2018Observational
- Structural Biology of the TNFα Antagonists Used in the Treatment of Rheumatoid Arthritis.International journal of molecular sciences · 2018Review
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adalimumab and Infliximab are recombinant IgG1 monoclonal antibodies (mAbs) that bind and neutralize human tumor necrosis factor alpha (TNFα). TNFα forms a stable homotrimer with unique surface-exposed sites for Adalimumab, Infliximab, and TNF receptor binding. Here, we report the structures of Adalimumab-TNFα and Infliximab-TNFα complexes modeled from negative stain EM and cryo-EM images. EM images reveal complex structures consisting of 1:1, 1:2, 2:2, and 3:2 complexes of Adalimumab-TNFα and Infliximab-TNFα. The 2:2 complex structures of Adalimumab-TNFα and Infliximab-TNFα show diamond-shaped profiles and the 2D class averages reveal distinct orientations of the Fab domains, indicating different binding modes by Adalimumab and Infliximab to TNFα. After separation by size exclusion chromatography and analysis by negative stain EM, the 3:2 complexes of Adalimumab-TNFα or Infliximab-TNFα complexes are more complicated but retain features recognized in the 2:2 complexes. Preliminary cryo-EM analysis of 3:2 Adalimumab-TNFα complex generated a low-resolution density consistent with a TNFα trimer bound with three Fab domains from three individual antibody molecules, while each antibody molecule binds to two molecules of TNFα trimer. The Fc domains are not visible in the reconstruction. These results show the two mAbs form structurally distinct complexes with TNFα.
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