8WQ5

Crystal structure of the C-terminal RRM domain of an RBP in complex with ssDNA

Summary for 8WQ5

• Entry DOI: 10.2210/pdb8wq5/pdb
• Related: 8WQ3
• Descriptor: RNA-binding protein 45, DNA (5'-D(*GP*AP*CP*GP*CP*AP*G)-3'), GLYCEROL, ... (4 entities in total)
• Functional Keywords: rbm45, rrm, als, ftld, rna binding protein/dna, rna binding protein-dna complex
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 61871.34

Authors

Chen, X.,Yang, Z.,Chen, X.,Wei, Q.,Guo, S.,Jiang, M.,Wang, M. (deposition date: 2023-10-11, release date: 2024-08-21, Last modification date: 2024-09-18)

Primary citation

Chen, X.,Wei, Q.,Yang, Z.,Chen, X.,Guo, S.,Jiang, M.,Wang, M.
Structural basis for RNA recognition by the C-terminal RRM domain of human RBM45.
J.Biol.Chem., 300:107640-107640, 2024

PubMed Abstract: RBM45 is an RNA-binding protein with roles in neural development by regulating RNA splicing. Its dysfunction and aggregation are associated with neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD). RBM45 harbors three RRM domains that potentially bind RNA. While the recognitions of RNA by its N-terminal tandem RRM domains (RRM1 and RRM2) have been well understood, the RNA-binding property of its C-terminal RRM (RRM3) remains unclear. In this work, we identified that the RRM3 of the RBM45 sequence specifically binds RNA with a GACG sequence, similar but not identical to those recognized by the RRM1 and RRM2. Further, we determined the crystal structure of RBM45 in complex with a GACG sequence-containing single-stranded DNA. Our structural results, together with the RNA-binding assays of mutants at key amino acid residues, revealed the molecular mechanism by which RBM45 recognizes an RNA sequence. Our finding on the RNA-binding property of the individual RRM module of RBM45 provides the foundation for unraveling the RNA-binding characteristics of full-length RBM45 and for understanding the biological functions of RBM45.

PubMed: 39122006
DOI: 10.1016/j.jbc.2024.107640

Experimental method

X-RAY DIFFRACTION (1.65 Å)