7BED

X-ray structure of WDR5 bound to the WDR5 win motif peptide

7BED の概要

• エントリーDOI: 10.2210/pdb7bed/pdb
• 分子名称: WD repeat-containing protein 5, SULFATE ION (3 entities in total)
• 機能のキーワード: wd repeat-containing protein 5 lana histone methyltransferase h3k4, transcription, transferase
• 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: 73366.94

構造登録者

McVey, C.E.,Kaye, K.M. (登録日: 2020-12-23, 公開日: 2021-12-08, 最終更新日: 2024-01-31)

主引用文献

Tan, M.,Li, S.,Juillard, F.,Chitas, R.,Custodio, T.F.,Xue, H.,Szymula, A.,Sun, Q.,Liu, B.,Alvarez, A.L.,Chen, S.,Huang, J.,Simas, J.P.,McVey, C.E.,Kaye, K.M.
MLL1 is regulated by KSHV LANA and is important for virus latency.
Nucleic Acids Res., 49:12895-12911, 2021

PubMed Abstract: Mixed lineage leukemia 1 (MLL1) is a histone methyltransferase. Kaposi's sarcoma-associated herpesvirus (KSHV) is a leading cause of malignancy in AIDS. KSHV latently infects tumor cells and its genome is decorated with epigenetic marks. Here, we show that KSHV latency-associated nuclear antigen (LANA) recruits MLL1 to viral DNA where it establishes H3K4me3 modifications at the extensive KSHV terminal repeat elements during primary infection. LANA interacts with MLL1 complex members, including WDR5, integrates into the MLL1 complex, and regulates MLL1 activity. We describe the 1.5-Å crystal structure of N-terminal LANA peptide complexed with MLL1 complex member WDR5, which reveals a potential regulatory mechanism. Disruption of MLL1 expression rendered KSHV latency establishment highly deficient. This deficiency was rescued by MLL1 but not by catalytically inactive MLL1. Therefore, MLL1 is LANA regulable and exerts a central role in virus infection. These results suggest broad potential for MLL1 regulation, including by non-host factors.

PubMed: 34850113
DOI: 10.1093/nar/gkab1094

実験手法

X-RAY DIFFRACTION (1.26 Å)