Structure

The nuclear pore complex, composed of proteins termed nucleoporins (Nups), is responsible for nucleocytoplasmic transport in eukaryotes. Nuclear pore complexes (NPCs) form an annular structure composed of the nuclear ring, cytoplasmic ring,\uc2\ua0a membrane ring, and two inner rings. Nup192 is\uc2\ua0a major component of the NPC's inner ring. We report the crystal structure of Saccharomyces cerevisiae Nup192 residues 2-960 [ScNup192(2-960)], which adopts an \uce\ub1-helical fold with three domains (i.e., D1, D2, and D3). Small angle X-ray scattering and electron microscopy (EM) studies reveal that ScNup192(2-960) could undergo long-range transition between "open" and "closed" conformations. We obtained a structural model of full-length ScNup192 based on EM, the structure of ScNup192(2-960), and homology modeling. Evolutionary analyses using the ScNup192(2-960) structure suggest that NPCs and vesicle-coating complexes are descended from a common membrane-coating ancestral complex. We show that suppression of Nup192 expression leads to compromised nuclear transport and hypothesize a role for Nup192 in modulating the permeability of the NPC central channel.C06 RR017528-01-CEM/CE/NCIPC CDC HHS/United StatesP30-EB-009998/EB/NIBIB NIH HHS/United StatesP41GM103393/GM/NIGMS NIH HHS/United StatesP41RR001209/RR/NCRR NIH HHS/United StatesR01 GM062427/GM/NIGMS NIH HHS/United StatesR01 GM071329/GM/NIGMS NIH HHS/United StatesR01 GM083960/GM/NIGMS NIH HHS/United StatesR01 GM083960/GM/NIGMS NIH HHS/United StatesU01 GM098256/GM/NIGMS NIH HHS/United StatesU01 GM098256/GM/NIGMS NIH HHS/United StatesU54 GM074945/GM/NIGMS NIH HHS/United StatesU54 GM094662/GM/NIGMS NIH HHS/United StatesU54 GM103511/GM/NIGMS NIH HHS/United StatesU54 GM103511/GM/NIGMS NIH HHS/United States2014-04-02T00:00:00Z23499021PMC375562