Abstract
Intrinsically disordered regions (IDRs) of proteins are implicated in key macromolecular interactions. However, the molecular forces underlying IDR function within multicomponent assemblies remain elusive. By combining thermodynamic and structural data, we have discovered an allostery-based mechanism regulating the soluble core region of the nuclear pore complex (NPC) composed of nucleoporins Nup53, Nic96, and Nup157. We have identified distinct IDRs in Nup53 that are functionally coupled when binding to partner nucleoporins and karyopherins (Kaps) involved in NPC assembly and nucleocytoplasmic transport. We show that the Nup53·Kap121 complex forms an ensemble of structures that destabilize Nup53 hub interactions. Our study provides a molecular framework for understanding how disordered and folded domains communicate within macromolecular complexes.
Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Allosteric Regulation
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Intrinsically Disordered Proteins / chemistry*
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Intrinsically Disordered Proteins / genetics
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Intrinsically Disordered Proteins / metabolism
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Membrane Transport Proteins / chemistry*
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Membrane Transport Proteins / genetics
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Membrane Transport Proteins / metabolism
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Multiprotein Complexes / chemistry*
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Multiprotein Complexes / genetics
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Multiprotein Complexes / metabolism
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Nuclear Pore / chemistry*
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Nuclear Pore / genetics
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Nuclear Pore / metabolism
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Nuclear Pore Complex Proteins / chemistry*
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Nuclear Pore Complex Proteins / genetics
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Nuclear Pore Complex Proteins / metabolism
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Protein Domains
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Receptors, Cytoplasmic and Nuclear / chemistry*
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / metabolism
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Saccharomyces cerevisiae / chemistry*
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins / chemistry*
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism
Substances
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Intrinsically Disordered Proteins
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Membrane Transport Proteins
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Multiprotein Complexes
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NUP53 protein, S cerevisiae
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Nuclear Pore Complex Proteins
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PSE1 protein, S cerevisiae
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Receptors, Cytoplasmic and Nuclear
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Saccharomyces cerevisiae Proteins