6N34

Crystal structure of the BTB domain of Human NS1-BP

6N34 の概要

• エントリーDOI: 10.2210/pdb6n34/pdb
• 分子名称: Influenza virus NS1A-binding protein (1 entity in total)
• 機能のキーワード: mrna export, splicing
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 33167.99

構造登録者

Zhang, K.,Shang, G.,Padavannil, A.,Fontoura, B.,Chook, Y.M. (登録日: 2018-11-14, 公開日: 2018-12-12, 最終更新日: 2023-10-11)

主引用文献

Zhang, K.,Shang, G.,Padavannil, A.,Wang, J.,Sakthivel, R.,Chen, X.,Kim, M.,Thompson, M.G.,Garcia-Sastre, A.,Lynch, K.W.,Chen, Z.J.,Chook, Y.M.,Fontoura, B.M.A.
Structural-functional interactions of NS1-BP protein with the splicing and mRNA export machineries for viral and host gene expression.
Proc. Natl. Acad. Sci. U.S.A., 115:E12218-E12227, 2018

PubMed Abstract: The influenza virulence factor NS1 protein interacts with the cellular NS1-BP protein to promote splicing and nuclear export of the viral M mRNAs. The viral M1 mRNA encodes the M1 matrix protein and is alternatively spliced into the M2 mRNA, which is translated into the M2 ion channel. These proteins have key functions in viral trafficking and budding. To uncover the NS1-BP structural and functional activities in splicing and nuclear export, we performed proteomics analysis of nuclear NS1-BP binding partners and showed its interaction with constituents of the splicing and mRNA export machineries. NS1-BP BTB domains form dimers in the crystal. Full-length NS1-BP is a dimer in solution and forms at least a dimer in cells. Mutations suggest that dimerization is important for splicing. The central BACK domain of NS1-BP interacts directly with splicing factors such as hnRNP K and PTBP1 and with the viral NS1 protein. The BACK domain is also the site for interactions with mRNA export factor Aly/REF and is required for viral M mRNA nuclear export. The crystal structure of the C-terminal Kelch domain shows that it forms a β-propeller fold, which is required for the splicing function of NS1-BP. This domain interacts with the polymerase II C-terminal domain and SART1, which are involved in recruitment of splicing factors and spliceosome assembly, respectively. NS1-BP functions are not only critical for processing a subset of viral mRNAs but also impact levels and nuclear export of a subset of cellular mRNAs encoding factors involved in metastasis and immunity.

PubMed: 30538201
DOI: 10.1073/pnas.1818012115

実験手法

X-RAY DIFFRACTION (2.8 Å)