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

Roman, Noelia, Christie, Mary, Swarbrick, Crystall M. D., Kobe, Bostjan and Forwood, Jade K. (2013) Structural characterisation of the nuclear import receptor importin alpha in complex with the bipartite NLS of Prp20. PLoS One, 8 12: e82038.1-e82038.6. doi:10.1371/journal.pone.0082038


Author Roman, Noelia
Christie, Mary
Swarbrick, Crystall M. D.
Kobe, Bostjan
Forwood, Jade K.
Title Structural characterisation of the nuclear import receptor importin alpha in complex with the bipartite NLS of Prp20
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-12-10
Year available 2013
Sub-type Article (original research)
DOI 10.1371/journal.pone.0082038
Open Access Status DOI
Volume 8
Issue 12
Start page e82038.1
End page e82038.6
Total pages 6
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Formatted 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-a (IMPa) adaptor protein, which in turn
binds to IMPb 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 2.1 A˚ resolution x-ray crystal structure of IMPa in complex with the NLS of Prp20. We observe 1,091 A˚2 of
buried surface area mediated by an extensive array of contacts involving residues on armadillo repeats 2-7, utilising both
the major and minor NLS binding sites of IMPa to contact bipartite NLS clusters 17RAKKMSK23 and 3
KR4, respectively. One notable feature of the major site is the insertion of Prp20NLS Ala18 between the P0 and P1 NLS sites, noted in only a few classical bipartite NLSs. This study provides a detailed account of the binding mechanism enabling Prp20 interaction with the nuclear import receptor, and additional new information for the interaction between IMPa and cargo.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
MULTIDISCIPLINARY SCIENCES
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Chemistry and Molecular Biosciences
Institute for Molecular Bioscience - Publications
 
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Created: Fri, 10 Jan 2014, 20:55:42 EST by Miss Abigail Downie on behalf of School of Chemistry & Molecular Biosciences