Lamina-associated polypeptide 2-alpha forms homo-trimers via its C terminus, and oligomerization is unaffected by a disease-causing mutation.

Abstract The nucleoplasmic protein, Lamina-associated polypeptide (LAP) 2α, is one of six alternatively spliced products of the LAP2gene, which share a common N-terminal region. In contrast to the other isoforms, which also share most of their C termini, LAP2α has a large unique C-terminal region that contains binding sites for chromatin, A-type lamins, and retinoblastoma protein. By immunoprecipitation analyses of LAP2α complexes from cells expressing differently tagged LAP2α proteins and fragments, we demonstrate that LAP2α forms higher order structures containing multiple LAP2α molecules in vivo and that complex formation is mediated by the C terminus. Solid phase binding assays using recombinant and in vitro translated LAP2α fragments showed direct interactions of LAP2α C termini. Cross-linking of LAP2α complexes and multiangle light scattering of purified LAP2α revealed the existence of stable homo-trimers in vivo and in vitro. Finally, we show that, in contrast to the LAP2α-lamin A interaction, its self-association is not affected by a disease-linked single point mutation in the LAP2α C terminus.