Implications of a Multiscale Structure of the Yeast Nuclear Pore Complex

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2023 Sep 22

PMID 37738963

Authors

Christopher W Akey

Ignacia Echeverria

Christna Ouch

Ilona Nudelman

Yi Shi

Junjie Wang

Brian T Chait

Andrej Sali

Javier Fernandez-Martinez

Michael P Rout

Affiliations

Soon will be listed here.

Abstract

Nuclear pore complexes (NPCs) direct the nucleocytoplasmic transport of macromolecules. Here, we provide a composite multiscale structure of the yeast NPC, based on improved 3D density maps from cryogenic electron microscopy and AlphaFold2 models. Key features of the inner and outer rings were integrated into a comprehensive model. We resolved flexible connectors that tie together the core scaffold, along with equatorial transmembrane complexes and a lumenal ring that anchor this channel within the pore membrane. The organization of the nuclear double outer ring reveals an architecture that may be shared with ancestral NPCs. Additional connections between the core scaffold and the central transporter suggest that under certain conditions, a degree of local organization is present at the periphery of the transport machinery. These connectors may couple conformational changes in the scaffold to the central transporter to modulate transport. Collectively, this analysis provides insights into assembly, transport, and NPC evolution.

Citing Articles

Frontiers in integrative structural modeling of macromolecular assemblies.

Majila K, Arvindekar S, Jindal M, Viswanath S QRB Discov. 2025; 6:e3.

PMID: 39944881 PMC: 11811862. DOI: 10.1017/qrd.2024.15.

Visualizing nuclear pore complex plasticity with Pan-Expansion Microscopy.

Morgan K, Carley E, Coyne A, Rothstein J, Lusk C, King M bioRxiv. 2024; .

PMID: 39345637 PMC: 11429769. DOI: 10.1101/2024.09.18.613744.

Docking a flexible basket onto the core of the nuclear pore complex.

Stankunas E, Kohler A Nat Cell Biol. 2024; 26(9):1504-1519.

PMID: 39138317 PMC: 11392808. DOI: 10.1038/s41556-024-01484-x.

The molecular architecture of the nuclear basket.

Singh D, Soni N, Hutchings J, Echeverria I, Shaikh F, Duquette M Cell. 2024; 187(19):5267-5281.e13.

PMID: 39127037 PMC: 11416316. DOI: 10.1016/j.cell.2024.07.020.

Nanoscale Quantitative Imaging of Single Nuclear Pore Complexes by Scanning Electrochemical Microscopy.

Chen R, Pathirathna P, Balla R, Kim J, Amemiya S Anal Chem. 2024; 96(26):10765-10771.

PMID: 38904303 PMC: 11223102. DOI: 10.1021/acs.analchem.4c01890.

References

von Appen A, Kosinski J, Sparks L, Ori A, DiGuilio A, Vollmer B . In situ structural analysis of the human nuclear pore complex. Nature. 2015; 526(7571):140-143. PMC: 4886846. DOI: 10.1038/nature15381. View

Kelley K, Knockenhauer K, Kabachinski G, Schwartz T . Atomic structure of the Y complex of the nuclear pore. Nat Struct Mol Biol. 2015; 22(5):425-431. PMC: 4424061. DOI: 10.1038/nsmb.2998. View

Burley S, Kurisu G, Markley J, Nakamura H, Velankar S, Berman H . PDB-Dev: a Prototype System for Depositing Integrative/Hybrid Structural Models. Structure. 2017; 25(9):1317-1318. PMC: 5821105. DOI: 10.1016/j.str.2017.08.001. View

Neumann N, Lundin D, Poole A . Comparative genomic evidence for a complete nuclear pore complex in the last eukaryotic common ancestor. PLoS One. 2010; 5(10):e13241. PMC: 2951903. DOI: 10.1371/journal.pone.0013241. View

Huang G, Zhan X, Zeng C, Liang K, Zhu X, Zhao Y . Cryo-EM structure of the inner ring from the Xenopus laevis nuclear pore complex. Cell Res. 2022; 32(5):451-460. PMC: 9061766. DOI: 10.1038/s41422-022-00633-x. View

Sampathkumar P, Ozyurt S, Do J, Bain K, Dickey M, Rodgers L . Structures of the autoproteolytic domain from the Saccharomyces cerevisiae nuclear pore complex component, Nup145. Proteins. 2010; 78(8):1992-8. PMC: 3136511. DOI: 10.1002/prot.22707. View

Terwilliger T, Poon B, Afonine P, Schlicksup C, Croll T, Millan C . Improved AlphaFold modeling with implicit experimental information. Nat Methods. 2022; 19(11):1376-1382. PMC: 9636017. DOI: 10.1038/s41592-022-01645-6. View

Yoshida K, Seo H, Debler E, Blobel G, Hoelz A . Structural and functional analysis of an essential nucleoporin heterotrimer on the cytoplasmic face of the nuclear pore complex. Proc Natl Acad Sci U S A. 2011; 108(40):16571-6. PMC: 3189060. DOI: 10.1073/pnas.1112846108. View

Petrovic S, Samanta D, Perriches T, Bley C, Thierbach K, Brown B . Architecture of the linker-scaffold in the nuclear pore. Science. 2022; 376(6598):eabm9798. PMC: 9867570. DOI: 10.1126/science.abm9798. View

10.

Terry L, Wente S . Flexible gates: dynamic topologies and functions for FG nucleoporins in nucleocytoplasmic transport. Eukaryot Cell. 2009; 8(12):1814-27. PMC: 2794212. DOI: 10.1128/EC.00225-09. View

11.

Andreu I, Granero-Moya I, Chahare N, Clein K, Molina-Jordan M, Beedle A . Mechanical force application to the nucleus regulates nucleocytoplasmic transport. Nat Cell Biol. 2022; 24(6):896-905. PMC: 7614780. DOI: 10.1038/s41556-022-00927-7. View

12.

Huang G, Zhan X, Zeng C, Zhu X, Liang K, Zhao Y . Cryo-EM structure of the nuclear ring from Xenopus laevis nuclear pore complex. Cell Res. 2022; 32(4):349-358. PMC: 8976044. DOI: 10.1038/s41422-021-00610-w. View

13.

Allegretti M, Zimmerli C, Rantos V, Wilfling F, Ronchi P, Fung H . In-cell architecture of the nuclear pore and snapshots of its turnover. Nature. 2020; 586(7831):796-800. DOI: 10.1038/s41586-020-2670-5. View

14.

Lim R, Huang N, Koser J, Deng J, Lau K, Schwarz-Herion K . Flexible phenylalanine-glycine nucleoporins as entropic barriers to nucleocytoplasmic transport. Proc Natl Acad Sci U S A. 2006; 103(25):9512-7. PMC: 1480438. DOI: 10.1073/pnas.0603521103. View

15.

Tang G, Peng L, Baldwin P, Mann D, Jiang W, Rees I . EMAN2: an extensible image processing suite for electron microscopy. J Struct Biol. 2006; 157(1):38-46. DOI: 10.1016/j.jsb.2006.05.009. View

16.

Mahamid J, Pfeffer S, Schaffer M, Villa E, Danev R, Kuhn Cuellar L . Visualizing the molecular sociology at the HeLa cell nuclear periphery. Science. 2016; 351(6276):969-72. DOI: 10.1126/science.aad8857. View

17.

Lim R, Huang B, Kapinos L . How to operate a nuclear pore complex by Kap-centric control. Nucleus. 2015; 6(5):366-72. PMC: 4915502. DOI: 10.1080/19491034.2015.1090061. View

18.

Kalita J, Kapinos L, Zheng T, Rencurel C, Zilman A, Lim R . Karyopherin enrichment and compensation fortifies the nuclear pore complex against nucleocytoplasmic leakage. J Cell Biol. 2022; 221(3). PMC: 8932525. DOI: 10.1083/jcb.202108107. View

19.

Brohawn S, Leksa N, Spear E, Rajashankar K, Schwartz T . Structural evidence for common ancestry of the nuclear pore complex and vesicle coats. Science. 2008; 322(5906):1369-73. PMC: 2680690. DOI: 10.1126/science.1165886. View

20.

Pettersen E, Goddard T, Huang C, Couch G, Greenblatt D, Meng E . UCSF Chimera--a visualization system for exploratory research and analysis. J Comput Chem. 2004; 25(13):1605-12. DOI: 10.1002/jcc.20084. View