6MX6

The Prp8 intein of Cryptococcus neoformans

6MX6 の概要

• エントリーDOI: 10.2210/pdb6mx6/pdb
• 分子名称: Pre-mRNA-processing-splicing factor 8 (2 entities in total)
• 機能のキーワード: prp8, intein, cryptococcus neoformans, hydrolase
• 由来する生物種: Cryptococcus neoformans var. grubii serotype A (strain H99 / ATCC 208821 / CBS 10515 / FGSC 9487)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 120554.84

構造登録者

Li, Z.,Li, H. (登録日: 2018-10-30, 公開日: 2019-10-23, 最終更新日: 2023-10-11)

主引用文献

Green, C.M.,Li, Z.,Smith, A.D.,Novikova, O.,Bacot-Davis, V.R.,Gao, F.,Hu, S.,Banavali, N.K.,Thiele, D.J.,Li, H.,Belfort, M.
Spliceosomal Prp8 intein at the crossroads of protein and RNA splicing.
Plos Biol., 17:e3000104-e3000104, 2019

PubMed Abstract: The spliceosome is a large ribonucleoprotein complex that removes introns from pre-mRNAs. At its functional core lies the essential pre-mRNA processing factor 8 (Prp8) protein. Across diverse eukaryotes, this protein cofactor of RNA catalysis harbors a self-splicing element called an intein. Inteins in Prp8 are extremely pervasive and are found at 7 different sites in various species. Here, we focus on the Prp8 intein from Cryptococcus neoformans (Cne), a human fungal pathogen. We solved the crystal structure of this intein, revealing structural homology among protein splicing sequences in eukaryotes, including the Hedgehog C terminus. Working with the Cne Prp8 intein in a reporter assay, we find that the biologically relevant divalent metals copper and zinc inhibit intein splicing, albeit by 2 different mechanisms. Copper likely stimulates reversible modifications on a catalytically important cysteine, whereas zinc binds at the terminal asparagine and the same critical cysteine. Importantly, we also show that copper treatment inhibits Prp8 protein splicing in Cne. Lastly, an intein-containing Prp8 precursor model is presented, suggesting that metal-induced protein splicing inhibition would disturb function of both Prp8 and the spliceosome. These results indicate that Prp8 protein splicing can be modulated, with potential functional implications for the spliceosome.

PubMed: 31600193
DOI: 10.1371/journal.pbio.3000104

実験手法

X-RAY DIFFRACTION (1.749 Å)