7TQA

Crystal Structure of monoclonal S9.6 Fab

7TQA の概要

• エントリーDOI: 10.2210/pdb7tqa/pdb
• 分子名称: Fab S9.6 heavy chain, Fab S9.6 light chain, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: antibody, fab, dna-rna hybrid, nucleic acid binding protein, ribonucleoprotein complex, immune system
• 由来する生物種: synthetic construct; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 148537.71

構造登録者

Bou-Nader, C.,Zhang, J. (登録日: 2022-01-26, 公開日: 2022-03-30, 最終更新日: 2024-11-06)

主引用文献

Bou-Nader, C.,Bothra, A.,Garboczi, D.N.,Leppla, S.H.,Zhang, J.
Structural basis of R-loop recognition by the S9.6 monoclonal antibody.
Nat Commun, 13:1641-1641, 2022

PubMed Abstract: R-loops are ubiquitous, dynamic nucleic-acid structures that play fundamental roles in DNA replication and repair, chromatin and transcription regulation, as well as telomere maintenance. The DNA-RNA hybrid-specific S9.6 monoclonal antibody is widely used to map R-loops. Here, we report crystal structures of a S9.6 antigen-binding fragment (Fab) free and bound to a 13-bp hybrid duplex. We demonstrate that S9.6 exhibits robust selectivity in binding hybrids over double-stranded (ds) RNA and in categorically rejecting dsDNA. S9.6 asymmetrically recognizes a compact epitope of two consecutive RNA nucleotides via their 2'-hydroxyl groups and six consecutive DNA nucleotides via their backbone phosphate and deoxyribose groups. Recognition is mediated principally by aromatic and basic residues of the S9.6 heavy chain, which closely track the curvature of the hybrid minor groove. These findings reveal the molecular basis for S9.6 recognition of R-loops, detail its binding specificity, identify a new hybrid-recognition strategy, and provide a framework for S9.6 protein engineering.

PubMed: 35347133
DOI: 10.1038/s41467-022-29187-7

実験手法

X-RAY DIFFRACTION (2.328 Å)