KAP1 is an antiparallel dimer with a 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 small ubiquitin mod...

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Veröffentlicht in:Life science alliance 2019-08, Vol.2 (4), p.e201900349
Hauptverfasser: Fonti, Giulia, Marcaida, Maria J, Bryan, Louise C, Träger, Sylvain, Kalantzi, Alexandra S, Helleboid, Pierre-Yves Jl, Demurtas, Davide, Tully, Mark D, Grudinin, Sergei, Trono, Didier, Fierz, Beat, Dal Peraro, Matteo
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Sprache:eng
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Zusammenfassung: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 small ubiquitin modifier ligase. This work sheds light on the overall organization of the full-length protein combining solution scattering data, integrative modeling, and single-molecule experiments. We show that KAP1 is an elongated antiparallel dimer with an asymmetry at the C-terminal domains. This conformation is consistent with the finding that the Really Interesting New Gene (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.
ISSN:2575-1077
2575-1077
DOI:10.26508/lsa.201900349