4C0P

Unliganded Transportin 3

4C0P の概要

• エントリーDOI: 10.2210/pdb4c0p/pdb
• 関連するPDBエントリー: 4C0O 4C0Q
• 分子名称: TRANSPORTIN-3, 2,3-DIHYDROXY-1,4-DITHIOBUTANE (2 entities in total)
• 機能のキーワード: transport protein, nuclear import, heat repeat, tnpo3
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Cytoplasm: Q9Y5L0
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 417741.60

構造登録者

Maertens, G.N.,Cook, N.J.,Hare, S.,Cherepanov, P. (登録日: 2013-08-06, 公開日: 2014-01-22, 最終更新日: 2023-12-20)

主引用文献

Maertens, G.N.,Cook, N.J.,Wang, W.,Hare, S.,Gupta, S.S.,Oztop, I.,Lee, K.,Pye, V.E.,Cosnefroy, O.,Snijders, A.P.,Kewalramani, V.N.,Fassati, A.,Engelman, A.,Cherepanov, P.
Structural Basis for Nuclear Import of Splicing Factors by Human Transportin 3.
Proc.Natl.Acad.Sci.USA, 111:2728-, 2014

PubMed Abstract: Transportin 3 (Tnpo3, Transportin-SR2) is implicated in nuclear import of splicing factors and HIV-1 replication. Herein, we show that the majority of cellular Tnpo3 binding partners contain arginine-serine (RS) repeat domains and present crystal structures of human Tnpo3 in its free as well as GTPase Ran- and alternative splicing factor/splicing factor 2 (ASF/SF2)-bound forms. The flexible β-karyopherin fold of Tnpo3 embraces the RNA recognition motif and RS domains of the cargo. A constellation of charged residues on and around the arginine-rich helix of Tnpo3 HEAT repeat 15 engage the phosphorylated RS domain and are critical for the recognition and nuclear import of ASF/SF2. Mutations in the same region of Tnpo3 impair its interaction with the cleavage and polyadenylation specificity factor 6 (CPSF6) and its ability to support HIV-1 replication. Steric incompatibility of the RS domain and RanGTP engagement by Tnpo3 provides the mechanism for cargo release in the nucleus. Our results elucidate the structural bases for nuclear import of splicing factors and the Tnpo3-CPSF6 nexus in HIV-1 biology.

PubMed: 24449914
DOI: 10.1073/PNAS.1320755111

実験手法

X-RAY DIFFRACTION (2.95 Å)