Format

Send to

Choose Destination
FEBS J. 2017 Jan;284(2):338-352. doi: 10.1111/febs.13983. Epub 2017 Jan 9.

Emerin self-assembly mechanism: role of the LEM domain.

Author information

1
Laboratory of Structural Biology and Radiobiology, Institute for Integrative Biology of the Cell (CEA, CNRS, University Paris South), University Paris-Saclay, Gif-sur-Yvette, France.
2
Department of Molecular Biophysics, Leibniz-Institut für Molekulare Pharmakologie, Berlin, Germany.
3
Center for Research in Myology (INSERM, CNRS), Université Pierre et Marie Curie Paris 06, Sorbonne Universités, France.
4
Department of Structural Virology, Institute for Integrative Biology of the Cell (CEA, CNRS, University Paris South), University Paris-Saclay, Gif-sur-Yvette, France.
5
Laboratory 'Innovative technologies for Detection and Diagnostics', Institute of Biology and Technology Saclay, CEA, Bagnols-sur-Cèze, France.
6
Institut für Biologie, Humboldt-Universität zu Berlin, Germany.

Abstract

At the nuclear envelope, the inner nuclear membrane protein emerin contributes to the interface between the nucleoskeleton and the chromatin. Emerin is an essential actor of the nuclear response to a mechanical signal. Genetic defects in emerin cause Emery-Dreifuss muscular dystrophy. It was proposed that emerin oligomerization regulates nucleoskeleton binding, and impaired oligomerization contributes to the loss of function of emerin disease-causing mutants. We here report the first structural characterization of emerin oligomers. We identified an N-terminal emerin region from amino acid 1 to amino acid 132 that is necessary and sufficient for formation of long curvilinear filaments. In emerin monomer, this region contains a globular LEM domain and a fragment that is intrinsically disordered. Solid-state nuclear magnetic resonance analysis identifies the LEM β-fragment as part of the oligomeric structural core. However, the LEM domain alone does not self-assemble into filaments. Additional residues forming a β-structure are observed within the filaments that could correspond to the unstructured region in emerin monomer. We show that the delK37 mutation causing muscular dystrophy triggers LEM domain unfolding and increases emerin self-assembly rate. Similarly, inserting a disulfide bridge that stabilizes the LEM folded state impairs emerin N-terminal region self-assembly, whereas reducing this disulfide bridge triggers self-assembly. We conclude that the LEM domain, responsible for binding to the chromatin protein BAF, undergoes a conformational change during self-assembly of emerin N-terminal region. The consequences of these structural rearrangement and self-assembly events on emerin binding properties are discussed.

KEYWORDS:

folding; intrinsically disordered region; lamin; nuclear envelope; nucleoskeleton; oligomerization

PMID:
27960036
DOI:
10.1111/febs.13983
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center