Molecular Events in Lamin B1 Homopolymerization: A Biophysical Characterization

Abstract

Lamin B1 is one of the major constituents of the nuclear lamina, a filamentous network underlying the nucleoplasmic side of the inner nuclear membrane. Homopolymerization of lamin B1, coupled to the homotypic and heterotypic association of other lamin types, is central to building the higher order network pattern inside the nucleus. This in turn maintains the mechanical and functional integrity of the lamina. We have characterized the molecular basis of the self-association of lamin B1 using spectroscopic and calorimetric methods. We report that concentration dependent lamin B1 oligomerization involves significant alterations in secondary and tertiary structures of the protein resulting in fairly observable compaction in size. Comparison of the energetics of the homotypic association of lamin B1 with that of lamin A reported earlier led to the finding that lamin A oligomers had higher thermodynamic stability. This leads us to conjecture that lamin B1 has less stress bearing ability compared to lamin A