Allosteric modulation of nucleoporin assemblies by intrinsically disordered regions.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31807700.
- Also identified by DOI 10.1126/sciadv.aax1836 and PMC identifier 6881172.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Intrinsically Disordered Proteins
- Membrane Transport Proteins
- Multiprotein Complexes
- Nuclear Pore
- Nuclear Pore Complex Proteins
- Receptors, Cytoplasmic and Nuclear
- Saccharomyces cerevisiae
- Saccharomyces cerevisiae Proteins