Fonti, GiuliaMarcaida, Maria J.Bryan, Louise C.Traeger, SylvainKalantzi, Alexandra S.Helleboid, Pierre-Yves J. L.Demurtas, DavideTully, Mark D.Grudinin, SergeiTrono, DidierFierz, BeatDal Peraro, Matteo2019-10-202019-10-202019-10-202019-08-0110.26508/lsa.201900349https://infoscience.epfl.ch/handle/20.500.14299/162122WOS:000484355500014KAP1 (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.BiologyLife Sciences & Biomedicine - Other Topicszinc-finger proteinstranscriptional corepressor tif1-betasmall-angle scatteringtripartite motife3 ligasestructural insightshp1 proteinstrim familycoiled-coilphd fingertext::journal::journal article::research article