KAP1 is an antiparallel dimer with a functional asymmetry

Life Sci Alliance. 2019 Aug 19;2(4):e201900349. doi: 10.26508/lsa.201900349. Print 2019 Aug.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Line
  • Chromatin / genetics
  • Chromatin / metabolism
  • Heterochromatin / genetics
  • Heterochromatin / metabolism
  • Humans
  • Promoter Regions, Genetic
  • Sumoylation
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Tripartite Motif-Containing Protein 28 / genetics
  • Tripartite Motif-Containing Protein 28 / metabolism*

Substances

  • Chromatin
  • Heterochromatin
  • Transcription Factors
  • TRIM28 protein, human
  • Tripartite Motif-Containing Protein 28

Associated data

  • PDB/6I9H
  • PDB/6O5K
  • PDB/2YVR
  • PDB/2RO1
  • PDB/1S4Z
  • PDB/1Q3L
  • PDB/2Y43
  • PDB/3DDT
  • PDB/3Q1D
  • PDB/4NQJ
  • PDB/2FMM
  • PDB/5AJ3