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Dissecting the Structural Dynamics of the Nuclear Pore Complex

42 Pages Posted: 20 May 2020 Sneak Peek Status: Under Review

See all articles by Zhanna Hakhverdyan

Zhanna Hakhverdyan

Rockefeller University - Laboratory of Cellular and Structural Biology

Kelly R. Molloy

Rockefeller University - Laboratory of Mass Spectrometry and Gaseous Ion Chemistry

Sarah Keegan

NYU Langone Health - Institute for Systems Genetics

Dante M. Lepore

University of Massachusetts Worcester - Department of Biochemistry and Cellular Pharmacology

Mary Munson

University of Massachusetts Worcester - Department of Biochemistry and Cellular Pharmacology

Roman I. Subbotin

Rockefeller University - Laboratory of Mass Spectrometry and Gaseous Ion Chemistry

David Fenyo

New York University (NYU) - School of Medicine

Javier Fernandez-Martinez

Rockefeller University - Laboratory of Cellular and Structural Biology

Brian T. Chait

Rockefeller University - Laboratory of Cellular and Structural Biology

Michael P. Rout

Rockefeller University - Laboratory of Cellular and Structural Biology

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Abstract

Cellular processes are largely carried out by macromolecular assemblies, most of which are dynamic, having components that are in constant flux. One such assembly is the nuclear pore complex (NPC), a ~50 MDa assembly comprised of ~30 different proteins termed Nups that mediates selective macromolecular transport between the nucleus and cytoplasm. We have developed a proteomic method to provide a comprehensive picture of the yeast NPC’s component dynamics. We discovered that while all Nups display a uniformly slow turnover, their exchange rates vary considerably. Surprisingly, this exchange rate was relatively unrelated to each Nup’s position, accessibility or role in transport, but rather correlated with its structural role; scaffold-forming Nups exchange slowly, while flexible connector Nups threading throughout the NPC’s architecture exchange more rapidly. Moreover, the cell has the capacity to destroy and replace a damaged Nup, regardless of apparent inaccessibility. Our approach provides a new window into macromolecular assembly dynamics.

Keywords: Macromolecular assembly, Protein complex, dynamics, Proteomics, Protein turnover, Protein exchange, Nuclear pore complex

Suggested Citation

Hakhverdyan, Zhanna and Molloy, Kelly R. and Keegan, Sarah and Lepore, Dante M. and Munson, Mary and Subbotin, Roman I. and Fenyo, David and Fernandez-Martinez, Javier and Chait, Brian T. and Rout, Michael P., Dissecting the Structural Dynamics of the Nuclear Pore Complex. CELL-D-20-01040. Available at SSRN: https://ssrn.com/abstract=3584516 or http://dx.doi.org/10.2139/ssrn.3584516
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Zhanna Hakhverdyan

Rockefeller University - Laboratory of Cellular and Structural Biology ( email )

United States

Kelly R. Molloy

Rockefeller University - Laboratory of Mass Spectrometry and Gaseous Ion Chemistry ( email )

United States

Sarah Keegan

NYU Langone Health - Institute for Systems Genetics ( email )

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Dante M. Lepore

University of Massachusetts Worcester - Department of Biochemistry and Cellular Pharmacology ( email )

55 N Lake Ave
Worcester, MA 01655
United States

Mary Munson

University of Massachusetts Worcester - Department of Biochemistry and Cellular Pharmacology

55 N Lake Ave
Worcester, MA 01655
United States

Roman I. Subbotin

Rockefeller University - Laboratory of Mass Spectrometry and Gaseous Ion Chemistry ( email )

United States

David Fenyo

New York University (NYU) - School of Medicine ( email )

550 First Ave.
VZ30, Office 626
New York, NY 10016
United States

Javier Fernandez-Martinez

Rockefeller University - Laboratory of Cellular and Structural Biology ( email )

United States

Brian T. Chait

Rockefeller University - Laboratory of Cellular and Structural Biology ( email )

United States

Michael P. Rout (Contact Author)

Rockefeller University - Laboratory of Cellular and Structural Biology

United States

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