Mapping the interaction between Trim28 and the KRAB domain at the center of Trim28 silencing of endogenous retroviruses

Autor:	Jamie R. H. Taka, Yunyuan Sun, David C. Goldstone
Rok vydání:	2022
Předmět:	Mammals Endogenous Retroviruses Zinc Fingers Tripartite Motif-Containing Protein 28 Biochemistry Chromatin Repressor Proteins Leucine Heterochromatin Animals Furylfuramide Molecular Biology Co-Repressor Proteins Transcription Factors
Zdroj:	Protein science : a publication of the Protein Society. 31(10)
ISSN:	1469-896X
Popis:	Transcription of endogenous retroviral elements are tightly regulated during development by members of the KRAB-containing zinc finger proteins (KRAB-ZFPs) and the co-repressor Trim28 (also known as Kap-1 or Tif1β). KRAB-ZFPs form the largest family of transcription regulators in mammals and initiate transcriptional silencing by tethering Trim28 to a target locus. Subsequently, Trim28 recruits chromatin modifying effectors resulting in the formation of heterochromatin. In the present study, we identify surface exposed residues on the central six turns of the Trim28 coiled-coil region forming the binding interface for the KRAB domain. Using AlphaFold2 (AF2) we provide high confidence models of the interface between Trim28 and the KRAB domain and identified leucine 301 on each chain of the Trim28 monomer to act as a pin extending into a hydrophobic pocket on the KRAB domain surface. Site directed mutations in the Trim28-KRAB binding interface abolished binding to the KRAB domain. Our work provides a detailed understanding of the specific interactions between the KRAB domain and the Trim28 coiled-coil and how this interaction may be regulated during silencing events.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::59ac4caa62994385aff314518b9d29af https://pubmed.ncbi.nlm.nih.gov/36173157 Zobrazit plný text záznamu Plný text