Molecular Architecture of the Major Membrane Ring Component of the Nuclear Pore Complex

The membrane ring that equatorially circumscribes the nuclear pore complex (NPC) in the perinuclear lumen of the nuclear envelope is composed largely of Pom152 in yeast and its ortholog Nup210 (or Gp210) in vertebrates. Here, we have used a combination of negative-stain electron microscopy, nuclear magnetic resonance, and small-angle X-ray scattering methods to determine an integrative structure of the ∼120 kDa luminal domain of Pom152. Our structural analysis reveals that the luminal domain is formed by a flexible string-of-pearls arrangement of nine repetitive cadherin-like Ig-like domains, indicating an evolutionary connection between NPCs and the cell adhesion machinery. The 16 copies of Pom152 known to be present in the yeast NPC are long enough to form the observed membrane ring, suggesting how interactions between Pom152 molecules help establish and maintain the NPC architecture. [Display omitted] •The Pom152 luminal domain is formed by 9 repeats of an Ig-like β-sandwich fold•Each Pom152 luminal repeat is a variant of the C3-subtype Ig-like fold family•Pom152 integrative structure suggests evolutionary relationship with cadherins We present the integrative molecular architecture of Pom152, the major component of the nuclear pore complex membrane ring. Pom152 is formed by a flexible string-of-pearls arrangement of nine repetitive cadherin-like Ig-like domains, indicating an evolutionary connection between NPCs and the cell adhesion machinery.