Interfacial binding and aggregation of lamin A tail domains associated with Hutchinson-Gilford progeria syndrome

Agnieszka Kalinowski, Peter N. Yaron, Zhao Qin, Siddharth Shenoy, Markus J. Buehler, Mathias Lösche, Kris Noel Dahl

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Hutchinson-Gilford progeria syndrome is a premature aging disorder associated with the expression of Δ50 lamin A (Δ50LA), a mutant form of the nuclear structural protein lamin A (LA). Δ50LA is missing 50 amino acids from the tail domain and retains a C-terminal farnesyl group that is cleaved from the wild-type LA. Many of the cellular pathologies of HGPS are thought to be a consequence of protein-membrane association mediated by the retained farnesyl group. To better characterize the protein-membrane interface, we quantified binding of purified recombinant Δ50LA tail domain (Δ50LA-TD) to tethered bilayer membranes composed of phosphatidylserine and phosphocholine using surface plasmon resonance. Farnesylated Δ50LA-TD binds to the membrane interface only in the presence of Ca2 + or Mg2 + at physiological ionic strength. At extremely low ionic strength, both the farnesylated and non-farnesylated forms of Δ50LA-TD bind to the membrane surface in amounts that exceed those expected for a densely packed protein monolayer. Interestingly, the wild-type LA-TD with no farnesylation also associates with membranes at low ionic strength but forms only a single layer. We suggest that electrostatic interactions are mediated by charge clusters with a net positive charge that we calculate on the surface of the LA-TDs. These studies suggest that the accumulation of Δ50LA at the inner nuclear membrane observed in cells is due to a combination of aggregation and membrane association rather than simple membrane binding; electrostatics plays an important role in mediating this association.

Original languageEnglish (US)
Pages (from-to)43-48
Number of pages6
JournalBiophysical Chemistry
StatePublished - Dec 2014
Externally publishedYes


  • Farnesylation
  • Hutchinson-Gilford progeria syndrome
  • Lamin A
  • Protein-membrane

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Organic Chemistry


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