8YWR

Crystal structure of the Fab fragment of the anti-IL-6 antibody 68F2 in complex with a domain-swapped IL-6 dimer

Summary for 8YWR

• Entry DOI: 10.2210/pdb8ywr/pdb
• Descriptor: Interleukin-6, Heavy chain of the Fab fragment of anti-IL-6 antibody 68F2, Light chain of the Fab fragment of anti-IL-6 antibody 68F2, ... (5 entities in total)
• Functional Keywords: interleukin, dimer, swap, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 66634.52

Authors

Bukhdruker, S.,Yudenko, A.,Borshchevskiy, V. (deposition date: 2024-03-31, release date: 2024-11-06, Last modification date: 2025-01-15)

Primary citation

Yudenko, A.,Bukhdruker, S.,Shishkin, P.,Rodin, S.,Burtseva, A.,Petrov, A.,Pigareva, N.,Sokolov, A.,Zinovev, E.,Eliseev, I.,Remeeva, A.,Marin, E.,Mishin, A.,Gordeliy, V.,Gushchin, I.,Ischenko, A.,Borshchevskiy, V.
Structural basis of signaling complex inhibition by IL-6 domain-swapped dimers.
Structure, 33:171-180.e5, 2025

PubMed Abstract: Interleukin-6 (IL-6) is a multifaceted cytokine essential in many immune system processes and their regulation. It also plays a key role in hematopoiesis, and in triggering the acute phase reaction. IL-6 overproduction is critical in chronic inflammation associated with autoimmune diseases like rheumatoid arthritis and contributes to cytokine storms in COVID-19 patients. Over 20 years ago, researchers proposed that IL-6, which is typically monomeric, can also form dimers via a domain-swap mechanism, with indirect evidence supporting their existence. The physiological significance of IL-6 dimers was shown in B-cell chronic lymphocytic leukemia. However, no structures have been reported so far. Here, we present the crystal structure of an IL-6 domain-swapped dimer that computational approaches could not predict. The structure explains why the IL-6 dimer is antagonistic to the IL-6 monomer in signaling complex formation and provides insights for IL-6 targeted therapies.

PubMed: 39566503
DOI: 10.1016/j.str.2024.10.028

Experimental method

X-RAY DIFFRACTION (2.93 Å)