7evr | pdb_00007evr
Crystal structure of hnRNP L RRM2 in complex with SETD2
Structural highlights
FunctionHNRPL_HUMAN Splicing factor binding to exonic or intronic sites and acting as either an activator or repressor of exon inclusion. Exhibits a binding preference for CA-rich elements. Component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes and associated with most nascent transcripts. Associates, together with APEX1, to the negative calcium responsive element (nCaRE) B2 of the APEX2 promoter.[1] Publication Abstract from PubMedThe 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. Structural basis of the interaction between SETD2 methyltransferase and hnRNP L paralogs for governing co-transcriptional splicing.,Bhattacharya S, Wang S, Reddy D, Shen S, Zhang Y, Zhang N, Li H, Washburn MP, Florens L, Shi Y, Workman JL, Li F Nat Commun. 2021 Nov 8;12(1):6452. doi: 10.1038/s41467-021-26799-3. PMID:34750379[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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