KAP1 is an antiparallel dimer with a functional asymmetry
| Autor: | Louise C. Bryan, Pierre-Yves Helleboid, Matteo Dal Peraro, Giulia Fonti, Davide Demurtas, Didier Trono, Beat Fierz, Mark D. Tully, Alexandra Styliani Kalantzi, Sergei Grudinin, Sylvain Träger, Maria J. Marcaida |
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| Přispěvatelé: | Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL), Ecole Polytechnique Fédérale de Lausanne (EPFL), European Synchrotron Radiation Facility (ESRF), Algorithms for Modeling and Simulation of Nanosystems (NANO-D), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Laboratoire Jean Kuntzmann (LJK ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), School of Life Sciences [Lausanne], Université de Lausanne = University of Lausanne (UNIL), Algorithms for Modeling and Simulating Nanosystems [2018-...] (NANO-D-POST [2018-2020]), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Transcription
Genetic Health Toxicology and Mutagenesis SUMO protein Plant Science Tripartite Motif-Containing Protein 28 small-angle scattering 0302 clinical medicine Heterochromatin phd finger Promoter Regions Genetic hp1 proteins Research Articles Coiled coil 0303 health sciences Ecology biology Chemistry Chromatin 3. Good health Ubiquitin ligase [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biophysics transcriptional corepressor tif1-beta Research Article zinc-finger proteins Antiparallel (biochemistry) Biochemistry Genetics and Molecular Biology (miscellaneous) tripartite motif structural insights Cell Line 03 medical and health sciences coiled-coil Humans [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biochemistry [q-bio.BM] Transcription factor 030304 developmental biology Binding Sites trim family Sumoylation e3 ligase PHD finger biology.protein Biophysics Heterochromatin protein 1 [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] 030217 neurology & neurosurgery Transcription Factors |
| Zdroj: | Life Science Alliance Life Science Alliance, Life Science Alliance LLC, 2019, 2 (4), pp.e201900349. ⟨10.26508/lsa.201900349⟩ Life Science Alliance, 2019, 2 (4), pp.e201900349. ⟨10.26508/lsa.201900349⟩ 'Life Science Alliance ', vol: 2, pages: e201900349-1-e20190034916 (2019) |
| ISSN: | 2575-1077 |
| Popis: | This study reveals the architecture of human KAP1 by integrating molecular modeling with small-angle X-ray scattering and single-molecule experiments. KAP1 dimers feature a structural asymmetry at the C-terminal domains that has functional implications for recruitment of HP1. 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. |
| Databáze: | OpenAIRE |
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