TY - JOUR T1 - KAP1 is an antiparallel dimer with a functional asymmetry JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.201900349 VL - 2 IS - 4 SP - e201900349 AU - Giulia Fonti AU - Maria J Marcaida AU - Louise C Bryan AU - Sylvain Träger AU - Alexandra S Kalantzi AU - Pierre-Yves JL Helleboid AU - Davide Demurtas AU - Mark D Tully AU - Sergei Grudinin AU - Didier Trono AU - Beat Fierz AU - Matteo Dal Peraro Y1 - 2019/08/01 UR - https://www.life-science-alliance.org/content/2/4/e201900349.abstract N2 - 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. ER -