NLS公司
核定位序列
核运输
内输蛋白
核孔
信号肽
重组DNA
生物物理学
核蛋白
转运蛋白
化学
细胞生物学
基因
生物
生物化学
细胞核
核心
转录因子
作者
Akiko Eguchi,Hiroyuki Furusawa,Akira Yamamoto,Teruo Akuta,Mamoru Hasegawa,Yoshio Okahata,Mahito Nakanishi
标识
DOI:10.1016/j.jconrel.2005.02.019
摘要
The nuclear membrane is a tight barrier against the delivery of therapeutic genes into non-dividing tissue cells. Overcoming this barrier with the aid of peptidic nuclear localization signals (NLS) is crucial for improving the performance of synthetic gene-delivery vehicles. In this article, we examine the nuclear transport of lambda phage particles displaying various peptides containing the minimum NLS of SV40 T antigen on their surface. As the minimum NLS (PKKKRKV) is a binding domain to importin α, recombinant proteins and molecular conjugates containing this peptide accumulate into the nucleus efficiently. However, we find that the C-terminal and N-terminal structures besides the minimum NLS profoundly affect the efficiency of the nuclear transport of the phage particles as well as their binding capacity to importin α: either truncation of a few amino acid residues from the C-terminus or the replacement of the N-terminus with a FLAG- or c-myc-tag abolish both of these biological activities. The structure of the optimized NLS is unpredictable from conventional protein transport assay and from the structural analysis in silico. Our results reveal that the objects with 50 nm in diameter can pass through the nuclear pore complex when the optimized NLS is displayed at a sufficient density on their surface.
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