Structural and Calorimetric Studies Demonstrate that Xeroderma Pigmentosum Type G (XPG) Can Be Imported to the Nucleus by a Classical Nuclear Import Pathway via a Monopartite NLS Sequence

Journal of Molecular Biology
Andrea C de BarrosMarcos R M Fontes

Abstract

Xeroderma pigmentosum type G (XPG) proteins are involved in DNA lesion recognition and promotion of nucleotide excision repair. Specific mutations in these proteins may lead to Cockayne syndrome, in which the patients may display severe developmental retardation and neurological abnormalities. No structural information is available for their spacer region or the C-terminal domain, which are important, respectively, for specific nucleotide excision repair activity and substrate specificity, as well as nuclear translocation. Immunofluorescence studies suggested two specific regions of the XPG C-terminus as potential bipartite nuclear localization sequences, which would be responsible for its translocation to the nucleus by the classical nuclear import pathway mediated by the importin-α (Impα). Thus, in order to test these hypotheses and gain insight into the structural basis for the nuclear import process for the XPG protein, we solved the crystal structures of complexes formed by the Impα and peptides corresponding to both putative nuclear localization signal (NLS) sequences (XPG1 and XPG2) and performed isothermal titration calorimetry assays to determine their binding affinities. Structural experiments confirm the binding of b...Continue Reading

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Citations

Jun 4, 2016·PloS One·Marcos Tadeu GeraldoNey Lemke
Jun 23, 2018·Traffic·Thomas W KirbyRobert E London
Oct 22, 2017·The Biochemical Journal·Natália E BernardesMarcos R M Fontes
Jun 10, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Xinli GuoKehai Liu
Apr 2, 2016·The Journal of Biological Chemistry·Rajeshwer S SankhalaGino Cingolani
May 12, 2017·Scientific Reports·K M SmithJ K Forwood

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