PUA domain
| PUA domain | |
|---|---|
 Cartoon representation of the molecular structure of the crystal structure of the PUA domain-containing protein APE0525 from Aeropyrum pernix HB8 (PDB: 2cx1) | |
| Identifiers | |
| Symbol | PUA |
| Pfam clan | CL0178 |
| ECOD | 1.1.9 |
In molecular biology, the PUA domain (Pseudouridine synthase and Archaeosine transglycosylase domain) is an ancient RNA-binding domain.[1]
Structure
[edit]The PUA domain consists of 64-96 amino acids forming a compact alpha/beta fold. It shows six beta-strands and two alpha-helices that cap the structure.[2]
Function
[edit]The PUA domain is found in diverse protein families[1] involved in:
- RNA modification: pseudouridine synthases, archaeosine transglycosylases, RNA methyltransferases
- Ribosome biogenesis: H/ACA box ribonucleoproteins, telomerase complex components
- Translation: eukaryotic initiation factors
- Metabolism: glutamate kinases (proline biosynthesis)
RNA recognition mechanism
[edit]The PUA domain uses a distinctive "double-edged ledge" formed by the alpha1-beta2 loop and beta6 strand for RNA binding while an "adjacent cleft" alpha1-beta2 accommodates single-stranded RNA overhangs. It has two main binding modes: the sideways binding recognizes minor groove of double-stranded RNA stems; and the terminal binding recognizes the bottom/terminal end of RNA stems across the major groove.[1]
Evolution and distribution
[edit]Proteins with the PUA domain are found across bacteria, archaea, and eukaryotes. This domain has evolved as a flexible RNA interaction module, with different proteins using variations in amino acid composition to achieve specific RNA recognition patterns while maintaining the core structural framework.[1]
Clinical Relevance
[edit]PUA domain proteins are essential for fundamental cellular processes.[2] Some examples of associated diseases are:
- Mutations in the protein Dyskerin lead to telomere dysfunction (dyskeratosis congenita)[3]
- MCT1 is implicated in cancer through its role in cell proliferation[4]
- Nsun6 mutations can lead to intellectual disability[5]
References
[edit]- ^ a b c d Pérez-Arellano, Isabel; Gallego, José; Cervera, Javier (2007). "The PUA domain - a structural and functional overview". The FEBS Journal. 274 (19): 4972–4984. doi:10.1111/j.1742-4658.2007.06031.x. ISSN 1742-464X. PMID 17803682.
- ^ a b Cerrudo, Carolina S.; Ghiringhelli, Pablo D.; Gomez, Daniel E. (2014). "Protein universe containing a PUA RNA-binding domain". The FEBS Journal. 281 (1): 74–87. doi:10.1111/febs.12602. ISSN 1742-4658. PMID 24393395.
- ^ Garus, Alexandre; Autexier, Chantal (2021). "Dyskerin: an essential pseudouridine synthase with multifaceted roles in ribosome biogenesis, splicing, and telomere maintenance". RNA (New York, N.Y.). 27 (12): 1441–1458. doi:10.1261/rna.078953.121. ISSN 1469-9001. PMC 8594475. PMID 34556550.
- ^ Silva, Ana; Cerqueira, Mónica Costa; Rosa, Beatriz; Sobral, Catarina; Pinto-Ribeiro, Filipa; Costa, Marta Freitas; Baltazar, Fátima; Afonso, Julieta (2023-03-07). "Prognostic Value of Monocarboxylate Transporter 1 Overexpression in Cancer: A Systematic Review". International Journal of Molecular Sciences. 24 (6): 5141. doi:10.3390/ijms24065141. ISSN 1422-0067. PMC 10049181. PMID 36982217.
- ^ Mattioli, Francesca; Worpenberg, Lina; Li, Cai-Tao; Ibrahim, Nazia; Naz, Shagufta; Sharif, Saima; Firouzabadi, Saghar G.; Vosoogh, Shohreh; Saraeva-Lamri, Radoslava; Raymond, Laure; Trujillo, Carlos; Guex, Nicolas; Antonarakis, Stylianos E.; Ansar, Muhammad; Darvish, Hossein (2023). "Biallelic variants in NSUN6 cause an autosomal recessive neurodevelopmental disorder". Genetics in Medicine: Official Journal of the American College of Medical Genetics. 25 (9): 100900. doi:10.1016/j.gim.2023.100900. ISSN 1530-0366. PMID 37226891.