8P6I

Crystal structure of the 139H2 Fab fragment bound to Muc1 peptide epitope

8P6I の概要

• エントリーDOI: 10.2210/pdb8p6i/pdb
• 分子名称: Mucin-1, 139H2 HC, 139H2 LC, ... (4 entities in total)
• 機能のキーワード: fab fragment, peptide complex, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 101628.80

構造登録者

Beugelink, J.W.,Peng, W.,Siborova, M.,Pronker, M.F.,Snijder, J.,Janssen, B.J.C. (登録日: 2023-05-26, 公開日: 2024-04-03, 最終更新日: 2024-10-16)

主引用文献

Peng, W.,Giesbers, K.C.,Siborova, M.,Beugelink, J.W.,Pronker, M.F.,Schulte, D.,Hilkens, J.,Janssen, B.J.,Strijbis, K.,Snijder, J.
Reverse-engineering the anti-MUC1 antibody 139H2 by mass spectrometry-based de novo sequencing.
Life Sci Alliance, 7:-, 2024

PubMed Abstract: Mucin 1 (MUC1) is a transmembrane mucin expressed at the apical surface of epithelial cells at mucosal surfaces. MUC1 has a barrier function against bacterial invasion and is well known for its aberrant expression and glycosylation in adenocarcinomas. The MUC1 extracellular domain contains a variable number of tandem repeats (VNTR) of 20 amino acids, which are heavily -linked glycosylated. Monoclonal antibodies against the MUC1 VNTR are powerful research tools with applications in the diagnosis and treatment of MUC1-expressing cancers. Here, we report direct mass spectrometry-based sequencing of anti-MUC1 hybridoma-derived 139H2 IgG, enabling reverse-engineering of the functional recombinant monoclonal antibody. The crystal structure of the 139H2 Fab fragment in complex with the MUC1 epitope was solved, revealing the molecular basis of 139H2 binding specificity to MUC1 and its tolerance to -glycosylation of the VNTR. The available sequence of 139H2 will allow further development of MUC1-related diagnostic, targeting, and treatment strategies.

PubMed: 38508723
DOI: 10.26508/lsa.202302366

実験手法

X-RAY DIFFRACTION (2.5 Å)