RT Journal Article
SR Electronic
T1 KAP1 is an antiparallel dimer with a functional asymmetry
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201900349
DO 10.26508/lsa.201900349
VO 2
IS 4
A1 Giulia Fonti
A1 Maria J Marcaida
A1 Louise C Bryan
A1 Sylvain Träger
A1 Alexandra S Kalantzi
A1 Pierre-Yves JL Helleboid
A1 Davide Demurtas
A1 Mark D Tully
A1 Sergei Grudinin
A1 Didier Trono
A1 Beat Fierz
A1 Matteo Dal Peraro
YR 2019
UL https://www.life-science-alliance.org/content/2/4/e201900349.abstract
AB 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.