2M16

P75/LEDGF PWWP Domain

2M16 の概要

• エントリーDOI: 10.2210/pdb2m16/pdb
• 関連するPDBエントリー: 2M15
• NMR情報: BMRB: 18478
• 分子名称: PC4 and SFRS1-interacting protein (1 entity in total)
• 機能のキーワード: protein, pwwp domain, transcription, dna binding
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: O75475
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11031.59

構造登録者

Crowe, B.L.,Foster, M.P. (登録日: 2012-11-18, 公開日: 2013-02-27, 最終更新日: 2024-05-15)

主引用文献

Eidahl, J.O.,Crowe, B.L.,North, J.A.,McKee, C.J.,Shkriabai, N.,Feng, L.,Plumb, M.,Graham, R.L.,Gorelick, R.J.,Hess, S.,Poirier, M.G.,Foster, M.P.,Kvaratskhelia, M.
Structural basis for high-affinity binding of LEDGF PWWP to mononucleosomes.
Nucleic Acids Res., 41:3924-3936, 2013

PubMed Abstract: Lens epithelium-derived growth factor (LEDGF/p75) tethers lentiviral preintegration complexes (PICs) to chromatin and is essential for effective HIV-1 replication. LEDGF/p75 interactions with lentiviral integrases are well characterized, but the structural basis for how LEDGF/p75 engages chromatin is unknown. We demonstrate that cellular LEDGF/p75 is tightly bound to mononucleosomes (MNs). Our proteomic experiments indicate that this interaction is direct and not mediated by other cellular factors. We determined the solution structure of LEDGF PWWP and monitored binding to the histone H3 tail containing trimethylated Lys36 (H3K36me3) and DNA by NMR. Results reveal two distinct functional interfaces of LEDGF PWWP: a well-defined hydrophobic cavity, which selectively interacts with the H3K36me3 peptide and adjacent basic surface, which non-specifically binds DNA. LEDGF PWWP exhibits nanomolar binding affinity to purified native MNs, but displays markedly lower affinities for the isolated H3K36me3 peptide and DNA. Furthermore, we show that LEDGF PWWP preferentially and tightly binds to in vitro reconstituted MNs containing a tri-methyl-lysine analogue at position 36 of H3 and not to their unmodified counterparts. We conclude that cooperative binding of the hydrophobic cavity and basic surface to the cognate histone peptide and DNA wrapped in MNs is essential for high-affinity binding to chromatin.

PubMed: 23396443
DOI: 10.1093/nar/gkt074

実験手法

SOLUTION NMR