Structural characterisation of the nuclear import receptor importin alpha in complex with the bipartite NLS of Prp20

PloS One
Noelia RomanJade K Forwood

Abstract

The translocation of macromolecules into the nucleus is a fundamental eukaryotic process, regulating gene expression, cell division and differentiation, but which is impaired in a range of significant diseases including cancer and viral infection. The import of proteins into the nucleus is generally initiated by a specific, high affinity interaction between nuclear localisation signals (NLSs) and nuclear import receptors in the cytoplasm, and terminated through the disassembly of these complexes in the nucleus. For classical NLSs (cNLSs), this import is mediated by the importin-α (IMPα) adaptor protein, which in turn binds to IMPβ to mediate translocation of nuclear cargo across the nuclear envelope. The interaction and disassembly of import receptor:cargo complexes is reliant on the differential localisation of nucleotide bound Ran across the envelope, maintained in its low affinity, GDP-bound form in the cytoplasm, and its high affinity, GTP-bound form in the nucleus. This in turn is maintained by the differential localisation of Ran regulating proteins, with RanGAP in the cytoplasm maintaining Ran in its GDP-bound form, and RanGEF (Prp20 in yeast) in the nucleus maintaining Ran in its GTP-bound form. Here, we describe the 2....Continue Reading

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Citations

Nov 3, 2015·Journal of Molecular Biology·Mary ChristieBostjan Kobe
Feb 7, 2015·The Biochemical Journal·Ruth A Pumroy, Gino Cingolani
Aug 19, 2015·PloS One·Ortal Amber-VitosYossi Tsfadia
Jul 17, 2015·Molecular Biology of the Cell·Annemarie KraltLiesbeth M Veenhoff
Oct 22, 2017·The Biochemical Journal·Natália E BernardesMarcos R M Fontes
Apr 2, 2016·The Journal of Biological Chemistry·Rajeshwer S SankhalaGino Cingolani
Jul 15, 2015·The Biochemical Journal·Michael Soniat, Yuh Min Chook
Jul 21, 2017·Cell Cycle·Kyle M LoftusSozanne R Solmaz
Oct 7, 2020·Viral Immunology·Camilla M DonnellyJade K Forwood
Jan 6, 2021·Nature Communications·Bikshapathi JaggaJade K Forwood

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Methods Mentioned

BETA
size exclusion chromatography
nucleotide exchange

Software Mentioned

BLU
COOT
REFMAC
iMOSFLM
ICE
Truncate
Scala
MosFlm
PROCHECK

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