9GEK
Structure of the FAST1-FAST2-RAP module from human FASTKD4 by carrier-driven crystallisation with maltose binding protein from E. coli.
Summary for 9GEK
| Entry DOI | 10.2210/pdb9gek/pdb |
| Descriptor | Maltose/maltodextrin-binding periplasmic protein,FAST kinase domain-containing protein 4,FAST kinase domain-containing protein 4, 3,6,9,12,15,18-HEXAOXAICOSANE-1,20-DIOL, PHOSPHATE ION, ... (6 entities in total) |
| Functional Keywords | mitochondrial rna splicing, rna stability, rna binding, mitochondrial disease, rna binding protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 1 |
| Total formula weight | 81252.29 |
| Authors | Hothorn, M.,Lau, K.,Yang, X. (deposition date: 2024-08-07, release date: 2025-01-15, Last modification date: 2025-03-19) |
| Primary citation | Yang, X.,Stentenbach, M.,Hughes, L.A.,Siira, S.J.,Lau, K.,Hothorn, M.,Martinou, J.C.,Rackham, O.,Filipovska, A. The Vsr-like protein FASTKD4 regulates the stability and polyadenylation of the MT-ND3 mRNA. Nucleic Acids Res., 53:-, 2025 Cited by PubMed Abstract: Expression of the compact mitochondrial genome is regulated by nuclear encoded, mitochondrially localized RNA-binding proteins (RBPs). RBPs regulate the lifecycles of mitochondrial RNAs from transcription to degradation by mediating RNA processing, maturation, stability and translation. The Fas-activated serine/threonine kinase (FASTK) family of RBPs has been shown to regulate and fine-tune discrete aspects of mitochondrial gene expression. Although the roles of specific targets of FASTK proteins have been elucidated, the molecular mechanisms of FASTK proteins in mitochondrial RNA metabolism remain unclear. Therefore, we resolved the structure of FASTKD4 at atomic level that includes the RAP domain and the two FAST motifs, creating a positively charged cavity resembling that of the very short patch repair endonuclease. Our biochemical studies show that FASTKD4 binds the canonical poly(A) tail of MT-ND3 enabling its maturation and translation. The in vitro role of FASTKD4 is consistent with its loss in cells that results in decreased MT-ND3 polyadenylation, which destabilizes this messenger RNA in mitochondria. PubMed: 39727163DOI: 10.1093/nar/gkae1261 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.15 Å) |
Structure validation
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