5e6q

Publication Abstract from PubMed

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 alpha (Impalpha) 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 Impalpha 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 Impalpha facilitates unloading by providing a partially complexed intermediate that is available for competitive binding by Nup50 or the Importin beta binding domain. This behavior provides a basis for meeting the intrinsically conflicting high affinity and high flux requirements of an efficient nuclear transport system.

Nuclear Localization of the DNA Repair Scaffold XRCC1: Uncovering the Functional Role of a Bipartite NLS.,Kirby TW, Gassman NR, Smith CE, Pedersen LC, Gabel SA, Sobhany M, Wilson SH, London RE Sci Rep. 2015 Aug 25;5:13405. doi: 10.1038/srep13405. PMID:26304019^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.