7EVR

Crystal structure of hnRNP L RRM2 in complex with SETD2

Summary for 7EVR

• Entry DOI: 10.2210/pdb7evr/pdb
• Descriptor: Heterogeneous nuclear ribonucleoprotein L, SHI domain from Histone-lysine N-methyltransferase SETD2 (3 entities in total)
• Functional Keywords: complex, rna binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 30828.80

Authors

Li, F.D.,Wang, S.M. (deposition date: 2021-05-22, release date: 2021-10-20, Last modification date: 2023-11-29)

Primary citation

Bhattacharya, S.,Wang, S.,Reddy, D.,Shen, S.,Zhang, Y.,Zhang, N.,Li, H.,Washburn, M.P.,Florens, L.,Shi, Y.,Workman, J.L.,Li, F.
Structural basis of the interaction between SETD2 methyltransferase and hnRNP L paralogs for governing co-transcriptional splicing.
Nat Commun, 12:6452-6452, 2021

PubMed Abstract: The RNA recognition motif (RRM) binds to nucleic acids as well as proteins. More than one such domain is found in the pre-mRNA processing hnRNP proteins. While the mode of RNA recognition by RRMs is known, the molecular basis of their protein interaction remains obscure. Here we describe the mode of interaction between hnRNP L and LL with the methyltransferase SETD2. We demonstrate that for the interaction to occur, a leucine pair within a highly conserved stretch of SETD2 insert their side chains in hydrophobic pockets formed by hnRNP L RRM2. Notably, the structure also highlights that RRM2 can form a ternary complex with SETD2 and RNA. Remarkably, mutating the leucine pair in SETD2 also results in its reduced interaction with other hnRNPs. Importantly, the similarity that the mode of SETD2-hnRNP L interaction shares with other related protein-protein interactions reveals a conserved design by which splicing regulators interact with one another.

PubMed: 34750379
DOI: 10.1038/s41467-021-26799-3

Experimental method

X-RAY DIFFRACTION (1.8 Å)