9NGX
Structure of the 5'SL-bound La Domain of the Human La-related Protein 6
Summary for 9NGX
| Entry DOI | 10.2210/pdb9ngx/pdb |
| NMR Information | BMRB: 31231 |
| Descriptor | La-related protein 6 (1 entity in total) |
| Functional Keywords | la, la-related protein, larp, larp6, collagen synthesis, fibrosis, rna binding protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 12639.46 |
| Authors | |
| Primary citation | Gordon, B.H.,Ogunkunle, V.S.,Silvers, R. Noncanonical RNA binding of human La-related protein 6. Nucleic Acids Res., 53:-, 2025 Cited by PubMed Abstract: La-related proteins (LARPs) are RNA-binding proteins that are involved in a variety of disease-related processes. Most LARPs recognize short single-stranded poly(U/A) motifs via a conserved hydrophobic pocket. Human LARP6 (HsLARP6) is an exception, binding a structured 5' stem-loop (5'SL) that controls type I collagen translation and fibroproliferative disease progression. Here, we present the de novo solution nuclear magnetic resonance structure of the La domain of HsLARP6 in the bound state. Chemical shift perturbation, solvent paramagnetic relaxation enhancement, intermolecular nuclear Overhauser effects, and targeted mutagenesis converge on a previously unknown binding interface that integrates electrostatic and hydrophobic contacts with shape complementarity in 5'SL binding. This noncanonical interface enables the La domain to discriminate 5'SL RNA from homopolymeric or purely helical hairpin RNAs with low-nanomolar affinity, overturning earlier views that the adjacent RNA recognition motif is required for recognition. The structure provides the first molecular model for 5'SL recognition and expands the paradigm of La-mediated RNA binding beyond 3'-terminal oligo-U/A motifs. These insights provide the biophysical framework for molecular recognition of 5'SL by LARP6 that is related to collagen biosynthesis in fibrosis and associated pathologies. PubMed: 40705921DOI: 10.1093/nar/gkaf682 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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