Structure of KAP1 tripartite motif identifies molecular interfaces required for retroelement silencing

DOI: 10.1073/pnas.1901318116

Authors: Guido A. Stoll (Medical Research Council Laboratory of Molecular Biology (MRC-LMB), University of Cambridge) , Shun-Ichiro Oda (Medical Research Council Laboratory of Molecular Biology (MRC-LMB)) , Zheng-Shan Chong (Medical Research Council Laboratory of Molecular Biology (MRC-LMB)) , Minmin Yu (Medical Research Council Laboratory of Molecular Biology (MRC-LMB)) , Stephen H. Mclaughlin (Medical Research Council Laboratory of Molecular Biology (MRC-LMB)) , Yorgo Modis (Medical Research Council Laboratory of Molecular Biology (MRC-LMB))
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Proceedings Of The National Academy Of Sciences , VOL 60

State: Published (Approved)
Published: July 2019
Diamond Proposal Number(s): 15916

Abstract: Retroviruses can integrate their DNA into the host-cell genome. Inherited retroviral DNA and other transposable elements account for more than half of the human genome. Transposable elements must be tightly regulated to restrict their proliferation and prevent toxic gene expression. KAP1/TRIM28 is an essential regulator of transposable element transcription. We determined the crystal structure of the KAP1 TRIM. The structure identifies a protein–protein interaction site required for recruitment of KAP1 to transposable elements. An epigenetic gene silencing assay confirms the importance of this site for KAP1-dependent silencing. We also show that KAP1 self-assembles in solution, but this self-assembly is not required for silencing. Our work provides insights into KAP1-dependent silencing and tools for expanding our mechanistic understanding of this process.

Diamond Keywords: Viruses; Epigenetics

Subject Areas: Biology and Bio-materials, Medicine


Instruments: I03-Macromolecular Crystallography

Added On: 16/07/2019 15:23

Documents:
1901318116.full.pdf

Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Genetics Structural biology Biophysics Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)