2mjh

From Proteopedia

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

Structural highlights

2mjh is a 2 chain structure with sequence from Caenorhabditis elegans. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GLD1_CAEEL Germ line-specific tumor suppressor essential for oogenesis. Controls the spatial pattern of translation of multiple oogenesis specific mRNAs (e.g. yolk receptor rme-2) by repression of translation during early meiotic prophase (leptotene to pachytene) and then derepression of translation during diplotene/ diakinesis, following its degradation. Also functions to promote the male sexual fate in the hermaphrodite germline but not the male germline. Functions redundantly with gld-2 to promote the initiation of meiotic development and/or inhibit stem cell proliferation.

Publication Abstract from PubMed

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 alpha-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.

Structural and functional implications of the QUA2 domain on RNA recognition by GLD-1.,Daubner GM, Brummer A, Tocchini C, Gerhardy S, Ciosk R, Zavolan M, Allain FH Nucleic Acids Res. 2014 May 16. pii: gku445. PMID:24838563^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Daubner GM, Brummer A, Tocchini C, Gerhardy S, Ciosk R, Zavolan M, Allain FH. Structural and functional implications of the QUA2 domain on RNA recognition by GLD-1. Nucleic Acids Res. 2014 May 16. pii: gku445. PMID:24838563 doi:http://dx.doi.org/10.1093/nar/gku445