title: The supramolecular organization of the C. elegans nuclear lamin filament.
abstract: Nuclear lamins are involved in most nuclear activities and are essential for retaining the mechano-elastic properties of the nucleus. They are nuclear intermediate filament (IF) proteins forming a distinct meshwork-like layer adhering to the inner nuclear membrane, called the nuclear lamina. Here, we present for the first time, the three-dimensional supramolecular organization of lamin 10 nm filaments and paracrystalline fibres. We show that Caenorhabditis elegans nuclear lamin forms 10 nm IF-like filaments, which are distinct from their cytoplasmic counterparts. The IF-like lamin filaments are composed of three and four tetrameric protofilaments, each of which contains two partially staggered anti-parallel head-to-tail polymers. The beaded appearance of the lamin filaments stems from paired globular tail domains, which are spaced regularly, alternating between 21 nm and 27 nm. A mutation in an evolutionarily conserved residue that causes Hutchison-Gilford progeria syndrome in humans alters the supramolecular structure of the lamin filaments. On the basis of our structural analysis, we propose an assembly pathway that yields the observed 10 nm IF-like lamin filaments and paracrystalline fibres. These results serve also as a platform for understanding the effect of laminopathic mutations on lamin supramolecular organization.
authors.affiliation: Department of Life Sciences, Ben Gurion University and the NIBN, Beer-Sheva, 84120 Israel.
authors.forename: Kfir
authors.initials: K
authors.lastname: Ben-Harush
authors.forename: Naama
authors.initials: N
authors.lastname: Wiesel
authors.forename: Daphna
authors.initials: D
authors.lastname: Frenkiel-Krispin
authors.forename: Dorothee
authors.initials: D
authors.lastname: Moeller
authors.forename: Eyal
authors.initials: E
authors.lastname: Soreq
authors.forename: Ueli
authors.initials: U
authors.lastname: Aebi
authors.forename: Harald
authors.initials: H
authors.lastname: Herrmann
authors.forename: Yosef
authors.initials: Y
authors.lastname: Gruenbaum
authors.forename: Ohad
authors.initials: O
authors.lastname: Medalia
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000235:genetics; D034882:Lamins / Q000737:chemistry* / Q000235:genetics; D034881:Nuclear Lamina / Q000737:chemistry
chemical_list: D029742:Caenorhabditis elegans Proteins; D034882:Lamins