Treffer: The cellular environment shapes the nuclear pore complex architecture.
Title:
The cellular environment shapes the nuclear pore complex architecture.
Authors:
Schuller AP; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA., Wojtynek M; Department of Biochemistry, University of Zurich, Zurich, Switzerland.; Department of Biology, Institute of Biochemistry, ETH Zurich, Zurich, Switzerland., Mankus D; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Tatli M; Department of Biochemistry, University of Zurich, Zurich, Switzerland., Kronenberg-Tenga R; Department of Biochemistry, University of Zurich, Zurich, Switzerland., Regmi SG; Division of Molecular and Cellular Biology, National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA., Dip PV; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.; MIT.nano, Massachusetts Institute of Technology, Cambridge, MA, USA., Lytton-Jean AKR; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Brignole EJ; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.; MIT.nano, Massachusetts Institute of Technology, Cambridge, MA, USA., Dasso M; Division of Molecular and Cellular Biology, National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA., Weis K; Department of Biology, Institute of Biochemistry, ETH Zurich, Zurich, Switzerland., Medalia O; Department of Biochemistry, University of Zurich, Zurich, Switzerland. omedalia@bioc.uzh.ch., Schwartz TU; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. tus@mit.edu.
Source:
Nature [Nature] 2021 Oct; Vol. 598 (7882), pp. 667-671. Date of Electronic Publication: 2021 Oct 13.
Publication Type:
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Language:
English
Journal Info:
Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE
Imprint Name(s):
Publication: Basingstoke : Nature Publishing Group
Original Publication: London, Macmillan Journals ltd.
Original Publication: London, Macmillan Journals ltd.
MeSH Terms:
Comments:
Comment in: Nat Cell Biol. 2021 Dec;23(12):1215. doi: 10.1038/s41556-021-00810-x. (PMID: 34876688)
Comment in: Mol Cell. 2021 Dec 16;81(24):4962-4963. doi: 10.1016/j.molcel.2021.11.029. (PMID: 34919818)
Comment in: Mol Cell. 2021 Dec 16;81(24):4962-4963. doi: 10.1016/j.molcel.2021.11.029. (PMID: 34919818)
References:
Grossman, E., Medalia, O. & Zwerger, M. Functional architecture of the nuclear pore complex. Annu. Rev. Biophys. 41, 557–584 (2012). (PMID: 2257782710.1146/annurev-biophys-050511-102328)
Knockenhauer, K. E. & Schwartz, T. U. The nuclear pore complex as a flexible and dynamic gate. Cell 164, 1162–1171 (2016). (PMID: 26967283478880910.1016/j.cell.2016.01.034)
Strambio-De-Castillia, C., Niepel, M. & Rout, M. P. The nuclear pore complex: bridging nuclear transport and gene regulation. Nat. Rev. Mol. Cell Biol. 11, 490–501 (2010). (PMID: 2057158610.1038/nrm2928)
Hampoelz, B., Andres-Pons, A., Kastritis, P. & Beck, M. Structure and assembly of the nuclear pore complex. Annu. Rev. Biophys. 48, 515–536 (2019). (PMID: 3094304410.1146/annurev-biophys-052118-115308)
Lin, D. H. & Hoelz, A. The structure of the nuclear pore complex (an update). Annu. Rev. Biochem. 88, 725–783 (2019). (PMID: 30883195658842610.1146/annurev-biochem-062917-011901)
Schwartz, T. U. The structure inventory of the nuclear pore complex. J. Mol. Biol. 428, 1986–2000 (2016). (PMID: 27016207488655110.1016/j.jmb.2016.03.015)
Fernandez-Martinez, J. & Rout, M. P. One ring to rule them all? Structural and functional diversity in the nuclear pore complex. Trends Biochem. Sci. https://doi.org/10.1016/j.tibs.2021.01.003 (2021).
Fernandez-Martinez, J. et al. Structure and function of the nuclear pore complex cytoplasmic mRNA export platform. Cell 167, 1215–1228 (2016). (PMID: 27839866513016410.1016/j.cell.2016.10.028)
Kosinski, J. et al. Molecular architecture of the inner ring scaffold of the human nuclear pore complex. Science 352, 363–365 (2016). (PMID: 2708107210.1126/science.aaf0643)
Kampmann, M. & Blobel, G. Three-dimensional structure and flexibility of a membrane-coating module of the nuclear pore complex. Nat. Struct. Mol. Biol. 16, 782–788 (2009). (PMID: 19503077270629610.1038/nsmb.1618)
Kelley, K., Knockenhauer, K. E., Kabachinski, G. & Schwartz, T. U. Atomic structure of the Y complex of the nuclear pore. Nat. Struct. Mol. Biol. 22, 425–431 (2015). (PMID: 25822992442406110.1038/nsmb.2998)
Bui, K. H. et al. Integrated structural analysis of the human nuclear pore complex scaffold. Cell 155, 1233–1243 (2013). (PMID: 2431509510.1016/j.cell.2013.10.055)
Lutzmann, M., Kunze, R., Buerer, A., Aebi, U. & Hurt, E. Modular self-assembly of a Y-shaped multiprotein complex from seven nucleoporins. EMBO J. 21, 387–397 (2002). (PMID: 1182343112582610.1093/emboj/21.3.387)
Stuwe, T. et al. Architecture of the nuclear pore complex coat. Science 347, 1148–1152 (2015). (PMID: 25745173518059210.1126/science.aaa4136)
von Appen, A. et al. In situ structural analysis of the human nuclear pore complex. Nature 526, 140–143 (2015). (PMID: 10.1038/nature15381)
Maimon, T., Elad, N., Dahan, I. & Medalia, O. The human nuclear pore complex as revealed by cryo-electron tomography. Structure 20, 998–1006 (2012). (PMID: 2263283410.1016/j.str.2012.03.025)
Villa, E., Schaffer, M., Plitzko, J. M. & Baumeister, W. Opening windows into the cell: focused-ion-beam milling for cryo-electron tomography. Curr. Opin. Struct. Biol. 23, 771–777 (2013). (PMID: 2409093110.1016/j.sbi.2013.08.006)
Allegretti, M. et al. In-cell architecture of the nuclear pore and snapshots of its turnover. Nature 586, 796–800 (2020). (PMID: 3287949010.1038/s41586-020-2670-5)
Zimmerli, C. E. et al. Nuclear pores constrict upon energy depletion. Preprint at https://doi.org/10.1101/2020.07.30.228585 (2020).
Mosalaganti, S. et al. In situ architecture of the algal nuclear pore complex. Nat. Commun. 9, 2361 (2018). (PMID: 29915221600642810.1038/s41467-018-04739-y)
Mahamid, J. et al. Visualizing the molecular sociology at the HeLa cell nuclear periphery. Science 351, 969–972 (2016). (PMID: 2691777010.1126/science.aad8857)
Zila, V. et al. Cone-shaped HIV-1 capsids are transported through intact nuclear pores. Cell 184, 1032–1046 (2021). (PMID: 33571428789589810.1016/j.cell.2021.01.025)
Regmi, S. G. et al. The nuclear pore complex consists of two independent scaffolds. Preprint at https://doi.org/10.1101/2020.11.13.381947 (2020).
Nordeen, S. A., Turman, D. L. & Schwartz, T. U. Yeast Nup84-Nup133 complex structure details flexibility and reveals conservation of the membrane anchoring ALPS motif. Nat. Commun. 11, 6060 (2020). (PMID: 33247142769569410.1038/s41467-020-19885-5)
Teimer, R., Kosinski, J., von Appen, A., Beck, M. & Hurt, E. A short linear motif in scaffold Nup145C connects Y-complex with pre-assembled outer ring Nup82 complex. Nat. Commun. 8, 1107 (2017). (PMID: 29062044565365110.1038/s41467-017-01160-9)
Eibauer, M. et al. Structure and gating of the nuclear pore complex. Nat. Commun. 6, 7532 (2015). (PMID: 2611270610.1038/ncomms8532)
Huang, G. et al. Structure of the cytoplasmic ring of the Xenopus laevis nuclear pore complex by cryo-electron microscopy single particle analysis. Cell Res. 30, 520–531 (2020). (PMID: 32376910726414610.1038/s41422-020-0319-4)
Hulsmann, B. B., Labokha, A. A. & Gorlich, D. The permeability of reconstituted nuclear pores provides direct evidence for the selective phase model. Cell 150, 738–751 (2012). (PMID: 2290180610.1016/j.cell.2012.07.019)
Kronenberg-Tenga, R. et al. A lamin A/C variant causing striated muscle disease provides insights into filament organization. J. Cell Sci. 134, jcs256156 (2021). (PMID: 3353624810.1242/jcs.256156)
Thaller, D. J. & Lusk, P. C. Fantastic nuclear envelope herniations and where to find them. Biochem. Soc. Trans. 46, 877–889 (2018). (PMID: 30026368619520010.1042/BST20170442)
Lin, D. H. et al. Architecture of the symmetric core of the nuclear pore. Science 352, aaf1015 (2016). (PMID: 27081075520720810.1126/science.aaf1015)
Sapra, K. T. et al. Nonlinear mechanics of lamin filaments and the meshwork topology build an emergent nuclear lamina. Nat. Commun. 11, 6205 (2020). (PMID: 33277502771891510.1038/s41467-020-20049-8)
Turgay, Y. et al. The molecular architecture of lamins in somatic cells. Nature 543, 261–264 (2017). (PMID: 28241138561621610.1038/nature21382)
Feldherr, C., Akin, D. & Moore, M. S. The nuclear import factor p10 regulates the functional size of the nuclear pore complex during oogenesis. J. Cell Sci. 111, 1889–1896 (1998). (PMID: 962575110.1242/jcs.111.13.1889)
Onischenko, E. et al. Natively unfolded FG repeats stabilize the structure of the nuclear pore complex. Cell 171, 904–917 (2017). (PMID: 29033133599232210.1016/j.cell.2017.09.033)
Kim, S. J. et al. Integrative structure and functional anatomy of a nuclear pore complex. Nature 555, 475–482 (2018). (PMID: 29539637602276710.1038/nature26003)
Ungricht, R. & Kutay, U. Establishment of NE asymmetry-targeting of membrane proteins to the inner nuclear membrane. Curr. Opin. Cell Biol. 34, 135–141 (2015). (PMID: 2611200210.1016/j.ceb.2015.04.005)
Meinema, A. C. et al. Long unfolded linkers facilitate membrane protein import through the nuclear pore complex. Science 333, 90–93 (2011). (PMID: 2165956810.1126/science.1205741)
Frey, S., Richter, R. P. & Gorlich, D. FG-rich repeats of nuclear pore proteins form a three-dimensional meshwork with hydrogel-like properties. Science 314, 815–817 (2006). (PMID: 1708245610.1126/science.1132516)
Frey, S. & Gorlich, D. A saturated FG-repeat hydrogel can reproduce the permeability properties of nuclear pore complexes. Cell 130, 512–523 (2007). (PMID: 1769325910.1016/j.cell.2007.06.024)
Ori, A. et al. Cell type-specific nuclear pores: a case in point for context-dependent stoichiometry of molecular machines. Mol. Syst. Biol. 9, 648 (2013). (PMID: 23511206361994210.1038/msb.2013.4)
, M. & D’Angelo, M. A. Nuclear pore complex composition: a new regulator of tissue-specific and developmental functions. Nat. Rev. Mol. Cell Biol. 13, 687–699 (2012). (PMID: 2309041410.1038/nrm3461)
Demircioglu, F. E. et al. The AAA + ATPase TorsinA polymerizes into hollow helical tubes with 8.5 subunits per turn. Nat. Commun. 10, 3262 (2019). (PMID: 31332180664635610.1038/s41467-019-11194-w)
Wagner, F. R. et al. Preparing samples from whole cells using focused-ion-beam milling for cryo-electron tomography. Nat. Protoc. 15, 2041–2070 (2020). (PMID: 32405053805342110.1038/s41596-020-0320-x)
Hagen, W. J. H., Wan, W. & Briggs, J. A. G. Implementation of a cryo-electron tomography tilt-scheme optimized for high resolution subtomogram averaging. J. Struct. Biol. 197, 191–198 (2017). (PMID: 27313000528735610.1016/j.jsb.2016.06.007)
Kremer, J. R., Mastronarde, D. N. & McIntosh, J. R. Computer visualization of three-dimensional image data using IMOD. J. Struct. Biol. 116, 71–76 (1996). (PMID: 874272610.1006/jsbi.1996.0013)
Forster, F., Medalia, O., Zauberman, N., Baumeister, W. & Fass, D. Retrovirus envelope protein complex structure in situ studied by cryo-electron tomography. Proc. Natl Acad. Sci. USA 102, 4729–4734 (2005). (PMID: 1577458055569010.1073/pnas.0409178102)
Beck, M., Lucic, V., Forster, F., Baumeister, W. & Medalia, O. Snapshots of nuclear pore complexes in action captured by cryo-electron tomography. Nature 449, 611–615 (2007). (PMID: 1785153010.1038/nature06170)
Scheres, S. H. RELION: implementation of a Bayesian approach to cryo-EM structure determination. J. Struct. Biol. 180, 519–530 (2012). (PMID: 23000701369053010.1016/j.jsb.2012.09.006)
Pettersen, E. F. et al. UCSF Chimera—a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004). (PMID: 1526425410.1002/jcc.20084)
Virtanen, P. et al. SciPy 1.0: fundamental algorithms for scientific computing in Python. Nat. Methods 17, 261–272 (2020). (PMID: 32015543705664410.1038/s41592-019-0686-2)
Seabold, S. & Perktold, J. statsmodels: econometric and statistical modeling with Python. In Proc. 9th Python in Science Conference (2010).
Hunter, J. D. Matplotlib: a 2D graphics environment. Comput. Sci. Eng. 9, 90–95 (2007). (PMID: 10.1109/MCSE.2007.55)
Nickell, S. et al. TOM software toolbox: acquisition and analysis for electron tomography. J. Struct. Biol. 149, 227–234 (2005). (PMID: 1572157610.1016/j.jsb.2004.10.006)
Knockenhauer, K. E. & Schwartz, T. U. The nuclear pore complex as a flexible and dynamic gate. Cell 164, 1162–1171 (2016). (PMID: 26967283478880910.1016/j.cell.2016.01.034)
Strambio-De-Castillia, C., Niepel, M. & Rout, M. P. The nuclear pore complex: bridging nuclear transport and gene regulation. Nat. Rev. Mol. Cell Biol. 11, 490–501 (2010). (PMID: 2057158610.1038/nrm2928)
Hampoelz, B., Andres-Pons, A., Kastritis, P. & Beck, M. Structure and assembly of the nuclear pore complex. Annu. Rev. Biophys. 48, 515–536 (2019). (PMID: 3094304410.1146/annurev-biophys-052118-115308)
Lin, D. H. & Hoelz, A. The structure of the nuclear pore complex (an update). Annu. Rev. Biochem. 88, 725–783 (2019). (PMID: 30883195658842610.1146/annurev-biochem-062917-011901)
Schwartz, T. U. The structure inventory of the nuclear pore complex. J. Mol. Biol. 428, 1986–2000 (2016). (PMID: 27016207488655110.1016/j.jmb.2016.03.015)
Fernandez-Martinez, J. & Rout, M. P. One ring to rule them all? Structural and functional diversity in the nuclear pore complex. Trends Biochem. Sci. https://doi.org/10.1016/j.tibs.2021.01.003 (2021).
Fernandez-Martinez, J. et al. Structure and function of the nuclear pore complex cytoplasmic mRNA export platform. Cell 167, 1215–1228 (2016). (PMID: 27839866513016410.1016/j.cell.2016.10.028)
Kosinski, J. et al. Molecular architecture of the inner ring scaffold of the human nuclear pore complex. Science 352, 363–365 (2016). (PMID: 2708107210.1126/science.aaf0643)
Kampmann, M. & Blobel, G. Three-dimensional structure and flexibility of a membrane-coating module of the nuclear pore complex. Nat. Struct. Mol. Biol. 16, 782–788 (2009). (PMID: 19503077270629610.1038/nsmb.1618)
Kelley, K., Knockenhauer, K. E., Kabachinski, G. & Schwartz, T. U. Atomic structure of the Y complex of the nuclear pore. Nat. Struct. Mol. Biol. 22, 425–431 (2015). (PMID: 25822992442406110.1038/nsmb.2998)
Bui, K. H. et al. Integrated structural analysis of the human nuclear pore complex scaffold. Cell 155, 1233–1243 (2013). (PMID: 2431509510.1016/j.cell.2013.10.055)
Lutzmann, M., Kunze, R., Buerer, A., Aebi, U. & Hurt, E. Modular self-assembly of a Y-shaped multiprotein complex from seven nucleoporins. EMBO J. 21, 387–397 (2002). (PMID: 1182343112582610.1093/emboj/21.3.387)
Stuwe, T. et al. Architecture of the nuclear pore complex coat. Science 347, 1148–1152 (2015). (PMID: 25745173518059210.1126/science.aaa4136)
von Appen, A. et al. In situ structural analysis of the human nuclear pore complex. Nature 526, 140–143 (2015). (PMID: 10.1038/nature15381)
Maimon, T., Elad, N., Dahan, I. & Medalia, O. The human nuclear pore complex as revealed by cryo-electron tomography. Structure 20, 998–1006 (2012). (PMID: 2263283410.1016/j.str.2012.03.025)
Villa, E., Schaffer, M., Plitzko, J. M. & Baumeister, W. Opening windows into the cell: focused-ion-beam milling for cryo-electron tomography. Curr. Opin. Struct. Biol. 23, 771–777 (2013). (PMID: 2409093110.1016/j.sbi.2013.08.006)
Allegretti, M. et al. In-cell architecture of the nuclear pore and snapshots of its turnover. Nature 586, 796–800 (2020). (PMID: 3287949010.1038/s41586-020-2670-5)
Zimmerli, C. E. et al. Nuclear pores constrict upon energy depletion. Preprint at https://doi.org/10.1101/2020.07.30.228585 (2020).
Mosalaganti, S. et al. In situ architecture of the algal nuclear pore complex. Nat. Commun. 9, 2361 (2018). (PMID: 29915221600642810.1038/s41467-018-04739-y)
Mahamid, J. et al. Visualizing the molecular sociology at the HeLa cell nuclear periphery. Science 351, 969–972 (2016). (PMID: 2691777010.1126/science.aad8857)
Zila, V. et al. Cone-shaped HIV-1 capsids are transported through intact nuclear pores. Cell 184, 1032–1046 (2021). (PMID: 33571428789589810.1016/j.cell.2021.01.025)
Regmi, S. G. et al. The nuclear pore complex consists of two independent scaffolds. Preprint at https://doi.org/10.1101/2020.11.13.381947 (2020).
Nordeen, S. A., Turman, D. L. & Schwartz, T. U. Yeast Nup84-Nup133 complex structure details flexibility and reveals conservation of the membrane anchoring ALPS motif. Nat. Commun. 11, 6060 (2020). (PMID: 33247142769569410.1038/s41467-020-19885-5)
Teimer, R., Kosinski, J., von Appen, A., Beck, M. & Hurt, E. A short linear motif in scaffold Nup145C connects Y-complex with pre-assembled outer ring Nup82 complex. Nat. Commun. 8, 1107 (2017). (PMID: 29062044565365110.1038/s41467-017-01160-9)
Eibauer, M. et al. Structure and gating of the nuclear pore complex. Nat. Commun. 6, 7532 (2015). (PMID: 2611270610.1038/ncomms8532)
Huang, G. et al. Structure of the cytoplasmic ring of the Xenopus laevis nuclear pore complex by cryo-electron microscopy single particle analysis. Cell Res. 30, 520–531 (2020). (PMID: 32376910726414610.1038/s41422-020-0319-4)
Hulsmann, B. B., Labokha, A. A. & Gorlich, D. The permeability of reconstituted nuclear pores provides direct evidence for the selective phase model. Cell 150, 738–751 (2012). (PMID: 2290180610.1016/j.cell.2012.07.019)
Kronenberg-Tenga, R. et al. A lamin A/C variant causing striated muscle disease provides insights into filament organization. J. Cell Sci. 134, jcs256156 (2021). (PMID: 3353624810.1242/jcs.256156)
Thaller, D. J. & Lusk, P. C. Fantastic nuclear envelope herniations and where to find them. Biochem. Soc. Trans. 46, 877–889 (2018). (PMID: 30026368619520010.1042/BST20170442)
Lin, D. H. et al. Architecture of the symmetric core of the nuclear pore. Science 352, aaf1015 (2016). (PMID: 27081075520720810.1126/science.aaf1015)
Sapra, K. T. et al. Nonlinear mechanics of lamin filaments and the meshwork topology build an emergent nuclear lamina. Nat. Commun. 11, 6205 (2020). (PMID: 33277502771891510.1038/s41467-020-20049-8)
Turgay, Y. et al. The molecular architecture of lamins in somatic cells. Nature 543, 261–264 (2017). (PMID: 28241138561621610.1038/nature21382)
Feldherr, C., Akin, D. & Moore, M. S. The nuclear import factor p10 regulates the functional size of the nuclear pore complex during oogenesis. J. Cell Sci. 111, 1889–1896 (1998). (PMID: 962575110.1242/jcs.111.13.1889)
Onischenko, E. et al. Natively unfolded FG repeats stabilize the structure of the nuclear pore complex. Cell 171, 904–917 (2017). (PMID: 29033133599232210.1016/j.cell.2017.09.033)
Kim, S. J. et al. Integrative structure and functional anatomy of a nuclear pore complex. Nature 555, 475–482 (2018). (PMID: 29539637602276710.1038/nature26003)
Ungricht, R. & Kutay, U. Establishment of NE asymmetry-targeting of membrane proteins to the inner nuclear membrane. Curr. Opin. Cell Biol. 34, 135–141 (2015). (PMID: 2611200210.1016/j.ceb.2015.04.005)
Meinema, A. C. et al. Long unfolded linkers facilitate membrane protein import through the nuclear pore complex. Science 333, 90–93 (2011). (PMID: 2165956810.1126/science.1205741)
Frey, S., Richter, R. P. & Gorlich, D. FG-rich repeats of nuclear pore proteins form a three-dimensional meshwork with hydrogel-like properties. Science 314, 815–817 (2006). (PMID: 1708245610.1126/science.1132516)
Frey, S. & Gorlich, D. A saturated FG-repeat hydrogel can reproduce the permeability properties of nuclear pore complexes. Cell 130, 512–523 (2007). (PMID: 1769325910.1016/j.cell.2007.06.024)
Ori, A. et al. Cell type-specific nuclear pores: a case in point for context-dependent stoichiometry of molecular machines. Mol. Syst. Biol. 9, 648 (2013). (PMID: 23511206361994210.1038/msb.2013.4)
, M. & D’Angelo, M. A. Nuclear pore complex composition: a new regulator of tissue-specific and developmental functions. Nat. Rev. Mol. Cell Biol. 13, 687–699 (2012). (PMID: 2309041410.1038/nrm3461)
Demircioglu, F. E. et al. The AAA + ATPase TorsinA polymerizes into hollow helical tubes with 8.5 subunits per turn. Nat. Commun. 10, 3262 (2019). (PMID: 31332180664635610.1038/s41467-019-11194-w)
Wagner, F. R. et al. Preparing samples from whole cells using focused-ion-beam milling for cryo-electron tomography. Nat. Protoc. 15, 2041–2070 (2020). (PMID: 32405053805342110.1038/s41596-020-0320-x)
Hagen, W. J. H., Wan, W. & Briggs, J. A. G. Implementation of a cryo-electron tomography tilt-scheme optimized for high resolution subtomogram averaging. J. Struct. Biol. 197, 191–198 (2017). (PMID: 27313000528735610.1016/j.jsb.2016.06.007)
Kremer, J. R., Mastronarde, D. N. & McIntosh, J. R. Computer visualization of three-dimensional image data using IMOD. J. Struct. Biol. 116, 71–76 (1996). (PMID: 874272610.1006/jsbi.1996.0013)
Forster, F., Medalia, O., Zauberman, N., Baumeister, W. & Fass, D. Retrovirus envelope protein complex structure in situ studied by cryo-electron tomography. Proc. Natl Acad. Sci. USA 102, 4729–4734 (2005). (PMID: 1577458055569010.1073/pnas.0409178102)
Beck, M., Lucic, V., Forster, F., Baumeister, W. & Medalia, O. Snapshots of nuclear pore complexes in action captured by cryo-electron tomography. Nature 449, 611–615 (2007). (PMID: 1785153010.1038/nature06170)
Scheres, S. H. RELION: implementation of a Bayesian approach to cryo-EM structure determination. J. Struct. Biol. 180, 519–530 (2012). (PMID: 23000701369053010.1016/j.jsb.2012.09.006)
Pettersen, E. F. et al. UCSF Chimera—a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004). (PMID: 1526425410.1002/jcc.20084)
Virtanen, P. et al. SciPy 1.0: fundamental algorithms for scientific computing in Python. Nat. Methods 17, 261–272 (2020). (PMID: 32015543705664410.1038/s41592-019-0686-2)
Seabold, S. & Perktold, J. statsmodels: econometric and statistical modeling with Python. In Proc. 9th Python in Science Conference (2010).
Hunter, J. D. Matplotlib: a 2D graphics environment. Comput. Sci. Eng. 9, 90–95 (2007). (PMID: 10.1109/MCSE.2007.55)
Nickell, S. et al. TOM software toolbox: acquisition and analysis for electron tomography. J. Struct. Biol. 149, 227–234 (2005). (PMID: 1572157610.1016/j.jsb.2004.10.006)
Grant Information:
R01 GM077537 United States GM NIGMS NIH HHS; R35 GM141834 United States GM NIGMS NIH HHS
Substance Nomenclature:
0 (Nuclear Pore Complex Proteins)
0 (nuclear pore complex protein 96)
0 (nuclear pore complex protein 96)
Entry Date(s):
Date Created: 20211014 Date Completed: 20220208 Latest Revision: 20230207
Update Code:
20250114
PubMed Central ID:
PMC8550940
DOI:
10.1038/s41586-021-03985-3
PMID:
34646014
Database:
MEDLINE
Weitere Informationen
Nuclear pore complexes (NPCs) create large conduits for cargo transport between the nucleus and cytoplasm across the nuclear envelope (NE) <sup>1-3</sup> . These multi-megadalton structures are composed of about thirty different nucleoporins that are distributed in three main substructures (the inner, cytoplasmic and nucleoplasmic rings) around the central transport channel <sup>4-6</sup> . Here we use cryo-electron tomography on DLD-1 cells that were prepared using cryo-focused-ion-beam milling to generate a structural model for the human NPC in its native environment. We show that-compared with previous human NPC models obtained from purified NEs-the inner ring in our model is substantially wider; the volume of the central channel is increased by 75% and the nucleoplasmic and cytoplasmic rings are reorganized. Moreover, the NPC membrane exhibits asymmetry around the inner-ring complex. Using targeted degradation of Nup96, a scaffold nucleoporin of the cytoplasmic and nucleoplasmic rings, we observe the interdependence of each ring in modulating the central channel and maintaining membrane asymmetry. Our findings highlight the inherent flexibility of the NPC and suggest that the cellular environment has a considerable influence on NPC dimensions and architecture.
(© 2021. The Author(s).)