7BCY

X-ray structure of WDR5delta24 bound to the Kaposi's sarcoma herpesvirus LANA win motif peptide

Summary for 7BCY

• Entry DOI: 10.2210/pdb7bcy/pdb
• Descriptor: WD repeat-containing protein 5, ORF 73 (3 entities in total)
• Functional Keywords: wd repeat-containing protein 5 lana histone methyltransferase h3k4, transcription, transferase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 71673.39

Authors

McVey, C.E.,Kaye, K.M. (deposition date: 2020-12-21, release date: 2021-12-08, Last modification date: 2024-11-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.5 Å)