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Biomolecular NMR Assignments

, Volume 12, Issue 2, pp 225–229 | Cite as

1H, 13C and 15N backbone resonance assignment of the lamin C-terminal region specific to prelamin A

  • Florian Celli
  • Ambre Petitalot
  • Camille Samson
  • François-Xavier Theillet
  • Sophie Zinn-Justin
Article
  • 76 Downloads

Abstract

Lamins are the main components of the nucleoskeleton. They form a protein meshwork that underlies the inner nuclear membrane. Mutations in the LMNA gene coding for A-type lamins (lamins A and C) cause a large panel of human diseases, referred to as laminopathies. These diseases include muscular dystrophies, lipodystrophies and premature aging diseases. Lamin A exhibits a C-terminal region that is different from lamin C and is post-translationally modified. It is produced as prelamin A and it is then farnesylated, cleaved, carboxymethylated and cleaved again in order to become mature lamin A. In patients with the severe Hutchinson–Gilford progeria syndrome, a specific single point mutation in LMNA leads to an aberrant splicing of the LMNA gene preventing the post-translational processing of prelamin A. This leads to the accumulation of a permanently farnesylated lamin A mutant lacking 50 amino acids named progerin. We here report the NMR 1H, 15N, 13CO, 13Cα and 13Cβ chemical shift assignment of the C-terminal region that is specific to prelamin A, from amino acid 567 to amino acid 664. We also report the NMR 1H, 15N, 13CO, 13Cα and 13Cβ chemical shift assignment of the C-terminal region of the progerin variant, from amino acid 567 to amino acid 614. Analysis of these chemical shift data confirms that both prelamin A and progerin C-terminal domains are largely disordered and identifies a common partially populated α-helix from amino acid 576 to amino acid 585. This helix is well conserved from fishes to mammals.

Keywords

Nuclear envelope Nucleoskeleton Intrinsically disordered protein NMR spectroscopy 

Notes

Acknowledgements

This work was supported by CEA, CNRS and University Paris South, by the French Infrastructure for Integrated Structural Biology (https://www.structuralbiology.eu/ networks/frisbi, Grant Number ANR-10-INSB-05-01, Acronym FRISBI) and by the French Association against Myopathies (AFM; research Grants Nos. 17243 and 20018 to S.Z.-J. and PhD fellowship No. 18159 to C.S.).

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© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institut de Biologie Intégrative de la Cellule (I2BC), CEA, CNRS, Univ. Paris Sud, Université Paris-SaclayGif-sur-YvetteFrance

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