Structure, dynamics, evolution, and function of a major scaffold component in the nuclear pore complex

Parthasarathy Sampathkumar, Seung Joong Kim, Paula Upla, William J. Rice, Jeremy Phillips, Benjamin L. Timney, Ursula Pieper, Jeffrey B. Bonanno, Javier Fernandez-Martinez, Zhanna Hakhverdyan, Natalia E. Ketaren, Tsutomu Matsui, Thomas M. Weiss, David L. Stokes, J. Michael Sauder, Stephen K. Burley, Andrej Sali, Michael P. Rout, Steven C. Almo

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

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, a membrane ring, and two inner rings. Nup192 is a 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 α-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.

Original languageEnglish (US)
Pages (from-to)560-571
Number of pages12
JournalStructure
Volume21
Issue number4
DOIs
StatePublished - Apr 2 2013

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Nuclear Pore
Saccharomyces cerevisiae
Nuclear Pore Complex Proteins
Cell Nucleus Active Transport
Electron Microscopy
Membranes
Structural Models
Eukaryota
Permeability
X-Rays

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

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Structure, dynamics, evolution, and function of a major scaffold component in the nuclear pore complex. / Sampathkumar, Parthasarathy; Kim, Seung Joong; Upla, Paula; Rice, William J.; Phillips, Jeremy; Timney, Benjamin L.; Pieper, Ursula; Bonanno, Jeffrey B.; Fernandez-Martinez, Javier; Hakhverdyan, Zhanna; Ketaren, Natalia E.; Matsui, Tsutomu; Weiss, Thomas M.; Stokes, David L.; Sauder, J. Michael; Burley, Stephen K.; Sali, Andrej; Rout, Michael P.; Almo, Steven C.

In: Structure, Vol. 21, No. 4, 02.04.2013, p. 560-571.

Research output: Contribution to journalArticle

Sampathkumar, P, Kim, SJ, Upla, P, Rice, WJ, Phillips, J, Timney, BL, Pieper, U, Bonanno, JB, Fernandez-Martinez, J, Hakhverdyan, Z, Ketaren, NE, Matsui, T, Weiss, TM, Stokes, DL, Sauder, JM, Burley, SK, Sali, A, Rout, MP & Almo, SC 2013, 'Structure, dynamics, evolution, and function of a major scaffold component in the nuclear pore complex', Structure, vol. 21, no. 4, pp. 560-571. https://doi.org/10.1016/j.str.2013.02.005
Sampathkumar, Parthasarathy ; Kim, Seung Joong ; Upla, Paula ; Rice, William J. ; Phillips, Jeremy ; Timney, Benjamin L. ; Pieper, Ursula ; Bonanno, Jeffrey B. ; Fernandez-Martinez, Javier ; Hakhverdyan, Zhanna ; Ketaren, Natalia E. ; Matsui, Tsutomu ; Weiss, Thomas M. ; Stokes, David L. ; Sauder, J. Michael ; Burley, Stephen K. ; Sali, Andrej ; Rout, Michael P. ; Almo, Steven C. / Structure, dynamics, evolution, and function of a major scaffold component in the nuclear pore complex. In: Structure. 2013 ; Vol. 21, No. 4. pp. 560-571.
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