1XK5

Crystal structure of the m3G-cap-binding domain of snurportin1 in complex with a m3GpppG-cap dinucleotide

Summary for 1XK5

• Entry DOI: 10.2210/pdb1xk5/pdb
• Descriptor: snurportin-1, 2,2,7-TRIMETHYL-GUANOSINE-5'-TRIPHOSPHATE-5'-GUANOSINE (3 entities in total)
• Functional Keywords: protein-rna-complex, transport protein
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: O95149
• Total number of polymer chains: 1
• Total formula weight: 23981.94

Authors

Strasser, A.,Dickmanns, A.,Luehrmann, R.,Ficner, R. (deposition date: 2004-09-27, release date: 2005-06-07, Last modification date: 2024-03-13)

Primary citation

Strasser, A.,Dickmanns, A.,Luehrmann, R.,Ficner, R.
Structural basis for m(3)G-cap-mediated nuclear import of spliceosomal UsnRNPs by snurportin1
Embo J., 24:2235-2243, 2005

PubMed Abstract: In higher eukaryotes the biogenesis of spliceosomal UsnRNPs involves a nucleocytoplasmic shuttling cycle. After the m7G-cap-dependent export of the snRNAs U1, U2, U4 and U5 to the cytoplasm, each of these snRNAs associates with seven Sm proteins. Subsequently, the m7G-cap is hypermethylated to the 2,2,7-trimethylguanosine (m3G)-cap. The import adaptor snurportin1 recognises the m3G-cap and facilitates the nuclear import of the UsnRNPs by binding to importin-beta. Here we report the crystal structure of the m3G-cap-binding domain of snurportin1 with bound m3GpppG at 2.4 A resolution, revealing a structural similarity to the mRNA-guanyly-transferase. Snurportin1 binds both the hypermethylated cap and the first nucleotide of the RNA in a stacked conformation. This binding mode differs significantly from that of the m7G-cap-binding proteins Cap-binding protein 20 (CBP20), eukaryotic initiation factor 4E (eIF4E) and viral protein 39 (VP39). The specificity of the m3G-cap recognition by snurportin1 was evaluated by fluorescence spectroscopy, demonstrating the importance of a highly solvent exposed tryptophan for the discrimination of m7G-capped RNAs. The critical role of this tryptophan and as well of a tryptophan continuing the RNA base stack was confirmed by nuclear import assays and cap-binding activity tests using several snurportin1 mutants.

PubMed: 15920472
DOI: 10.1038/sj.emboj.7600701

Experimental method

X-RAY DIFFRACTION (2.4 Å)