6GX9

Crystal structure of the TNPO3 - CPSF6 RSLD complex

6GX9 の概要

• エントリーDOI: 10.2210/pdb6gx9/pdb
• 分子名称: Transportin-3, Cleavage and polyadenylation specificity factor subunit 6, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: karyopherin-cargo complex, nuclear import, sr-like domain, nuclear protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 227920.07

構造登録者

Cherepanov, P.,Cook, N. (登録日: 2018-06-26, 公開日: 2019-03-13, 最終更新日: 2025-10-01)

主引用文献

Jang, S.,Cook, N.J.,Pye, V.E.,Bedwell, G.J.,Dudek, A.M.,Singh, P.K.,Cherepanov, P.,Engelman, A.N.
Differential role for phosphorylation in alternative polyadenylation function versus nuclear import of SR-like protein CPSF6.
Nucleic Acids Res., 47:4663-4683, 2019

PubMed Abstract: Cleavage factor I mammalian (CFIm) complex, composed of cleavage and polyadenylation specificity factor 5 (CPSF5) and serine/arginine-like protein CPSF6, regulates alternative polyadenylation (APA). Loss of CFIm function results in proximal polyadenylation site usage, shortening mRNA 3' untranslated regions (UTRs). Although CPSF6 plays additional roles in human disease, its nuclear translocation mechanism remains unresolved. Two β-karyopherins, transportin (TNPO) 1 and TNPO3, can bind CPSF6 in vitro, and we demonstrate here that while the TNPO1 binding site is dispensable for CPSF6 nuclear import, the arginine/serine (RS)-like domain (RSLD) that mediates TNPO3 binding is critical. The crystal structure of the RSLD-TNPO3 complex revealed potential CPSF6 interaction residues, which were confirmed to mediate TNPO3 binding and CPSF6 nuclear import. Both binding and nuclear import were independent of RSLD phosphorylation, though a hyperphosphorylated mimetic mutant failed to bind TNPO3 and mislocalized to the cell cytoplasm. Although hypophosphorylated CPSF6 largely supported normal polyadenylation site usage, a significant number of mRNAs harbored unnaturally extended 3' UTRs, similar to what is observed when other APA regulators, such as CFIIm component proteins, are depleted. Our results clarify the mechanism of CPSF6 nuclear import and highlight differential roles for RSLD phosphorylation in nuclear translocation versus regulation of APA.

PubMed: 30916345
DOI: 10.1093/nar/gkz206

実験手法

X-RAY DIFFRACTION (2.7 Å)