3D2S

Crystal structure of MBNL1 tandem zinc finger 3 and 4 domain in complex with CGCUGU RNA

Summary for 3D2S

• Entry DOI: 10.2210/pdb3d2s/pdb
• Related: 3D2N 3D2Q
• Descriptor: 5'-R(*CP*GP*CP*UP*GP*U)-3', Muscleblind-like protein 1, ZINC ION, ... (4 entities in total)
• Functional Keywords: tandem zinc finger domain, rna, metal-binding, nucleus, rna-binding, zinc-finger, metal binding protein-rna complex, metal binding protein/rna
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: 3D2S
• Total number of polymer chains: 8
• Total formula weight: 40672.60

Authors

Teplova, M.,Patel, D.J. (deposition date: 2008-05-08, release date: 2008-12-02, Last modification date: 2024-04-03)

Primary citation

Teplova, M.,Patel, D.J.
Structural insights into RNA recognition by the alternative-splicing regulator muscleblind-like MBNL1.
Nat.Struct.Mol.Biol., 15:1343-1351, 2008

PubMed Abstract: Muscleblind-like (MBNL) proteins, regulators of developmentally programmed alternative splicing, harbor tandem CCCH zinc-finger (ZnF) domains that target pre-mRNAs containing YGCU(U/G)Y sequence elements (where Y is a pyrimidine). In myotonic dystrophy, reduced levels of MBNL proteins lead to aberrant alternative splicing of a subset of pre-mRNAs. The crystal structure of MBNL1 ZnF3/4 bound to r(CGCUGU) establishes that both ZnF3 and ZnF4 target GC steps, with site-specific recognition mediated by a network of hydrogen bonds formed primarily with main chain groups of the protein. The relative alignment of ZnF3 and ZnF4 domains is dictated by the topology of the interdomain linker, with a resulting antiparallel orientation of bound GC elements, supportive of a chain-reversal loop trajectory for MBNL1-bound pre-mRNA targets. We anticipate that MBNL1-mediated targeting of looped RNA segments proximal to splice-site junctions could contribute to pre-mRNA alternative-splicing regulation.

PubMed: 19043415
DOI: 10.1038/nsmb.1519

Experimental method

X-RAY DIFFRACTION (1.7 Å)