Structural and functional characterisation of the KRAB-domain associated protein 1

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 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 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.


Advisor(s):
Dal Peraro, Matteo
Year:
2019
Publisher:
Lausanne, EPFL
Keywords:
Laboratories:
UPDALPE1




 Record created 2019-10-14, last modified 2019-10-14


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