7Z36

Crystal structure of the KAP1 tripartite motif in complex with the ZNF93 KRAB domain

7Z36 の概要

• エントリーDOI: 10.2210/pdb7z36/pdb
• 分子名称: Endolysin,Transcription intermediary factor 1-beta,Isoform 2 of Transcription intermediary factor 1-beta, SMARCAD1 CUE1 domain, Zinc finger protein 93, ... (4 entities in total)
• 機能のキーワード: transcription factor, trim family, krab domain, crispri, transcription
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 134606.91

構造登録者

Stoll, G.A.,Modis, Y. (登録日: 2022-03-01, 公開日: 2022-11-02, 最終更新日: 2024-01-31)

主引用文献

Stoll, G.A.,Pandiloski, N.,Douse, C.H.,Modis, Y.
Structure and functional mapping of the KRAB-KAP1 repressor complex.
Embo J., 41:e111179-e111179, 2022

PubMed Abstract: Transposable elements are a genetic reservoir from which new genes and regulatory elements can emerge. However, expression of transposable elements can be pathogenic and is therefore tightly controlled. KRAB domain-containing zinc finger proteins (KRAB-ZFPs) recruit the co-repressor KRAB-associated protein 1 (KAP1/TRIM28) to regulate many transposable elements, but how KRAB-ZFPs and KAP1 interact remains unclear. Here, we report the crystal structure of the KAP1 tripartite motif (TRIM) in complex with the KRAB domain from a human KRAB-ZFP, ZNF93. Structure-guided mutations in the KAP1-KRAB binding interface abolished repressive activity in an epigenetic transcriptional silencing assay. Deposition of H3K9me3 over thousands of loci is lost genome-wide in cells expressing a KAP1 variant with mutations that abolish KRAB binding. Our work identifies and functionally validates the KRAB-KAP1 molecular interface, which is critical for a central transcriptional control axis in vertebrates. In addition, the structure-based prediction of KAP1 recruitment efficiency will enable optimization of KRABs used in CRISPRi.

PubMed: 36341546
DOI: 10.15252/embj.2022111179

実験手法

X-RAY DIFFRACTION (2.8 Å)