4YHZ

Crystal structure of 304M3-B Fab in complex with H3K4me3 peptide

4YHZ の概要

• エントリーDOI: 10.2210/pdb4yhz/pdb
• 関連するPDBエントリー: 4YHP 4YHY
• 分子名称: Fab Heavy Chain, Fab Light Chain, H3K4me3 peptide, ... (6 entities in total)
• 機能のキーワード: antibody, fab, head-to-head dimerization, h3k4me3, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 50149.73

構造登録者

Hattori, T.,Dementieva, I.S.,Montano, S.P.,Koide, S. (登録日: 2015-02-27, 公開日: 2016-02-10, 最終更新日: 2023-09-27)

主引用文献

Hattori, T.,Lai, D.,Dementieva, I.S.,Montano, S.P.,Kurosawa, K.,Zheng, Y.,Akin, L.R.,Swist-Rosowska, K.M.,Grzybowski, A.T.,Koide, A.,Krajewski, K.,Strahl, B.D.,Kelleher, N.L.,Ruthenburg, A.J.,Koide, S.
Antigen clasping by two antigen-binding sites of an exceptionally specific antibody for histone methylation.
Proc.Natl.Acad.Sci.USA, 113:2092-2097, 2016

PubMed Abstract: Antibodies have a well-established modular architecture wherein the antigen-binding site residing in the antigen-binding fragment (Fab or Fv) is an autonomous and complete unit for antigen recognition. Here, we describe antibodies departing from this paradigm. We developed recombinant antibodies to trimethylated lysine residues on histone H3, important epigenetic marks and challenging targets for molecular recognition. Quantitative characterization demonstrated their exquisite specificity and high affinity, and they performed well in common epigenetics applications. Surprisingly, crystal structures and biophysical analyses revealed that two antigen-binding sites of these antibodies form a head-to-head dimer and cooperatively recognize the antigen in the dimer interface. This "antigen clasping" produced an expansive interface where trimethylated Lys bound to an unusually extensive aromatic cage in one Fab and the histone N terminus to a pocket in the other, thereby rationalizing the high specificity. A long-neck antibody format with a long linker between the antigen-binding module and the Fc region facilitated antigen clasping and achieved both high specificity and high potency. Antigen clasping substantially expands the paradigm of antibody-antigen recognition and suggests a strategy for developing extremely specific antibodies.

PubMed: 26862167
DOI: 10.1073/pnas.1522691113

実験手法

X-RAY DIFFRACTION (2.304 Å)