KAP1 is an antiparallel dimer with a natively functional asymmetry

KAP1 (KRAB-domain associated protein 1) plays a fundamental role in regulating gene expression in mammalian cells by recruiting different transcription factors and altering the chromatin state. In doing so, KAP1 acts both as a platform for macromolecular interactions and as an E3 SUMO ligase. This w...

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Published inbioRxiv
Main Authors Fonti, Giulia, Marcaida, Maria, Bryan, Louise, Traeger, Sylvain, Kalantzi, Alexandra, Pierre-Yves Helleboid, Demurtas, Davide, Tully, Mark, Grudinin, Sergei, Trono, Didier, Fierz, Beat, Matteo Dal Peraro
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 19.02.2019
Subjects
Asymmetry
Binding sites
Chromatin
Gene expression
Heterochromatin
Heterochromatin protein 1
Macromolecules
Mammalian cells
Protein structure
Proteins
Stoichiometry
SUMO protein
Transcription factors
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Summary:KAP1 (KRAB-domain associated protein 1) plays a fundamental role in regulating gene expression in mammalian cells by recruiting different transcription factors and altering the chromatin state. In doing so, KAP1 acts both as a platform for macromolecular interactions and as an E3 SUMO ligase. This work sheds light on the overall organization of the full-length protein combining solution scattering diffraction data, integrative modeling and single-molecule experiments. We show that KAP1 is an elongated antiparallel dimer with a native asymmetry at the C-terminal domain. This conformation supports our finding that the RING domain contributes to KAP1 auto-SUMOylation. Importantly, this intrinsic asymmetry has key functional implications for the KAP1 network of interactions, as the heterochromatin protein 1 (HP1) occupies only one of the two putative HP1 binding sites on the KAP1 dimer, resulting in an unexpected stoichiometry, even in the context of chromatin fibers.
DOI:10.1101/553511