3D2W

Crystal structure of mouse TDP-43 RRM2 domain in complex with DNA

Summary for 3D2W

• Entry DOI: 10.2210/pdb3d2w/pdb
• Descriptor: TAR DNA-binding protein 43, DNA (5'-D(*DGP*DTP*DTP*DGP*DAP*DGP*DCP*DGP*DTP*DT)-3'), PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: dp-43 proteinopathy, tdp-43 inclusions, rna recognition motif, ftld-u, als, rrm, dna-rna binding protein complex, dna/rna binding protein
• Biological source: Mus musculus (mouse); More
• Cellular location: Nucleus (By similarity): Q921F2
• Total number of polymer chains: 2
• Total formula weight: 13283.46

Authors

Kuo, P.H.,Yuan, H.S. (deposition date: 2008-05-09, release date: 2009-04-07, Last modification date: 2023-11-01)

Primary citation

Kuo, P.H.,Doudeva, L.G.,Wang, Y.T.,Shen, C.K.,Yuan, H.S.
Structural insights into TDP-43 in nucleic-acid binding and domain interactions
Nucleic Acids Res., 37:1799-1808, 2009

PubMed Abstract: TDP-43 is a pathogenic protein: its normal function in binding to UG-rich RNA is related to cystic fibrosis, and inclusion of its C-terminal fragments in brain cells is directly linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Here we report the 1.65 A crystal structure of the C-terminal RRM2 domain of TDP-43 in complex with a single-stranded DNA. We show that TDP-43 is a dimeric protein with two RRM domains, both involved in DNA and RNA binding. The crystal structure reveals the basis of TDP-43's TG/UG preference in nucleic acids binding. It also reveals that RRM2 domain has an atypical RRM-fold with an additional beta-strand involved in making protein-protein interactions. This self association of RRM2 domains produced thermal-stable RRM2 assemblies with a melting point greater than 85 degrees C as monitored by circular dichroism at physiological conditions. These studies thus characterize the recognition between TDP-43 and nucleic acids and the mode of RRM2 self association, and provide molecular models for understanding the role of TDP-43 in cystic fibrosis and the neurodegenerative diseases related to TDP-43 proteinopathy.

PubMed: 19174564
DOI: 10.1093/nar/gkp013

Experimental method

X-RAY DIFFRACTION (1.65 Å)