278126 Thermodynamic Properties of Nuclear Lamin Proteins

Wednesday, October 31, 2012
Hall B (Convention Center )
Kelli Coffey1, Matthew Biegler2, Agnieszka Kalinowski3 and Kris Noel Dahl1, (1)Chemical Engineering, Carnegie Mellon University, Pittsburgh, PA, (2)Materials Science and Engineering, Carnegie Mellon University, (3)Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA

The cell contains many filamentous network systems: the cytoskeleton is found throughout the cellular interior and the nucleoskeleton is found inside the inner nuclear membrane. The nucleoskeleton provides mechanical stability to the nucleus and aids in expression of genes. The nucleoskeleton is formed from independent networks of intermediate filaments primarily made of lamin A and lamin B proteins. There are numerous disease-causing mutations in lamin A, including the premature aging disorder Hutchison Gilford progeria syndrome (HGPS). A duplication of the lamin B gene LMNB1 causes adult-onset autosomal dominant leukodystrophy (ADLD), which is progressive neurological disorder. We have studied thermodynamic changes of the tail domain conformation of these proteins, since the tail domain is responsible for most of the protein-protein assocation.  We examine mature lamin B, mature lamin A, prelamin A and the mutant form of lamin A associated with HGPS, Δ50, by stepwise increases in temperature or changes in salt, and we analyzing the changes of the fluorescence of the tryptophan residues inside the the Ig-fold found in the tail domains. Temperature- and salt-induced changes the conformation of both prelamin A and Δ50 from a more to less compact form, and this conformational change is necessary for nuclear membrane association. The effective changes in thermodynamic stability may provide molecular insight into progression of nucleoskeletal disorders.

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