2MJH

Solution structure of the GLD-1 RNA-binding domain in complex with RNA

Summary for 2MJH

• Entry DOI: 10.2210/pdb2mjh/pdb
• NMR Information: BMRB: 19726
• Descriptor: Female germline-specific tumor suppressor gld-1, 5'-CUACUCAUAU-3' (2 entities in total)
• Functional Keywords: gld-1, kh-qua2 domain, star protein family, rna regulation, tra-2, rna binding protein
• Biological source: Caenorhabditis elegans (nematode)
• Total number of polymer chains: 2
• Total formula weight: 19158.41

Authors

Daubner, G.M.,Allain, F.H.-T. (deposition date: 2014-01-09, release date: 2014-05-28, Last modification date: 2024-05-15)

Primary citation

Daubner, G.M.,Brummer, A.,Tocchini, C.,Gerhardy, S.,Ciosk, R.,Zavolan, M.,Allain, F.H.
Structural and functional implications of the QUA2 domain on RNA recognition by GLD-1.
Nucleic Acids Res., 42:8092-8105, 2014

PubMed Abstract: The STAR family comprises ribonucleic acid (RNA)-binding proteins that play key roles in RNA-regulatory processes. RNA recognition is achieved by a KH domain with an additional α-helix (QUA2) that seems to extend the RNA-binding surface to six nucleotides for SF1 (Homo sapiens) and seven nucleotides for GLD-1 (Caenorhabditis elegans). To understand the structural basis of this probable difference in specificity, we determined the solution structure of GLD-1 KH-QUA2 with the complete consensus sequence identified in the tra-2 gene. Compared to SF1, the GLD-1 KH-QUA2 interface adopts a different conformation resulting indeed in an additional sequence-specific binding pocket for a uracil at the 5'end. The functional relevance of this binding pocket is emphasized by our bioinformatics analysis showing that GLD-1 binding sites with this 5'end uracil are more predictive for the functional response of the messenger RNAs to gld-1 knockout. We further reveal the importance of the KH-QUA2 interface in vitro and that its alteration in vivo affects the level of translational repression dependent on the sequence of the GLD-1 binding motif. In conclusion, we demonstrate that the QUA2 domain distinguishes GLD-1 from other members of the STAR family and contributes more generally to the modulation of RNA-binding affinity and specificity of KH domain containing proteins.

PubMed: 24838563
DOI: 10.1093/nar/gku445

Experimental method

SOLUTION NMR