5E6Q

Importin alpha binding to XRCC1 NLS peptide

5E6Q の概要

• エントリーDOI: 10.2210/pdb5e6q/pdb
• 分子名称: Importin subunit alpha-1, DNA repair protein XRCC1 NLS peptide, SULFATE ION, ... (6 entities in total)
• 機能のキーワード: xrcc1, importin, nls, bipartite, protein binding
• 由来する生物種: Mus musculus (Mouse); 詳細
• 細胞内の位置: Cytoplasm : P52293; Nucleus : P18887
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 59605.37

構造登録者

Pedersen, L.C.,Kirby, T.W.,Gassman, N.R.,Smith, C.E.,Gabel, S.A.,Sobhany, M.,Wilson, S.H.,London, R.E. (登録日: 2015-10-10, 公開日: 2015-10-28, 最終更新日: 2023-09-27)

主引用文献

Kirby, T.W.,Gassman, N.R.,Smith, C.E.,Pedersen, L.C.,Gabel, S.A.,Sobhany, M.,Wilson, S.H.,London, R.E.
Nuclear Localization of the DNA Repair Scaffold XRCC1: Uncovering the Functional Role of a Bipartite NLS.
Sci Rep, 5:13405-13405, 2015

PubMed Abstract: We have characterized the nuclear localization signal (NLS) of XRCC1 structurally using X-ray crystallography and functionally using fluorescence imaging. Crystallography and binding studies confirm the bipartite nature of the XRCC1 NLS interaction with Importin α (Impα) in which the major and minor binding motifs are separated by >20 residues, and resolve previous inconsistent determinations. Binding studies of peptides corresponding to the bipartite NLS, as well as its major and minor binding motifs, to both wild-type and mutated forms of Impα reveal pronounced cooperative binding behavior that is generated by the proximity effect of the tethered major and minor motifs of the NLS. The cooperativity stems from the increased local concentration of the second motif near its cognate binding site that is a consequence of the stepwise binding behavior of the bipartite NLS. We predict that the stepwise dissociation of the NLS from Impα facilitates unloading by providing a partially complexed intermediate that is available for competitive binding by Nup50 or the Importin β binding domain. This behavior provides a basis for meeting the intrinsically conflicting high affinity and high flux requirements of an efficient nuclear transport system.

PubMed: 26304019
DOI: 10.1038/srep13405

実験手法

X-RAY DIFFRACTION (2.305 Å)