7Z36
Crystal structure of the KAP1 tripartite motif in complex with the ZNF93 KRAB domain
Summary for 7Z36
| Entry DOI | 10.2210/pdb7z36/pdb |
| Descriptor | 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) |
| Functional Keywords | transcription factor, trim family, krab domain, crispri, transcription |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 5 |
| Total formula weight | 134606.91 |
| Authors | Stoll, G.A.,Modis, Y. (deposition date: 2022-03-01, release date: 2022-11-02, Last modification date: 2024-01-31) |
| Primary citation | 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 Cited by 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: 36341546DOI: 10.15252/embj.2022111179 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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