HUP domain
 | This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (April 2025) |
| HUP domain | |
|---|---|
 Cartoon representation of the molecular structure of the crystal structure of cysteinyl-tRNA synthetase from Escherichia coli with cysteine substrate bound (PDB: 1li7)[1] | |
| Identifiers | |
| Symbol | HUP |
| Pfam clan | CL0039 |
| ECOD | 2005.1 |
In molecular biology the HUP domain, often referred to as Rossmann-like or Rossmannoid,[2] is a nucleotide binding domain that catalyses adenylation reactions through the release of pyrophosphate and plays critical roles in various enzymatic functions, including aminoacyl-tRNA synthesis and biosynthesis of cofactors like NAD, FAD, and CoA.[3][4]
Structure
[edit]The HUP domain adopts a Rossmann-like fold, consisting of a five-stranded parallel β-sheet in a 5-4-1-2-3 configuration surrounded by α-helices.[4][5]
Function
[edit]The HUP domain catalyses adenylation reactions through the release of pyrophosphate. It binds nucleotides, particularly adenine-based molecules like ATP or AMP, with ribose binding being its most conserved feature.[3] Proteins containing this domain show great functional diversity: HUP domains are found in both enzymatic and non-enzymatic proteins, with functions ranging from aminoacyl-tRNA synthesis to electron transfer. This broad functional spectrum is unusual for nucleotide binding domains.[4]
Functional subgroups
[edit]The domain is found in proteins with a wide variety of multidomain architectures, which contribute to its functional versatility.[6] The HUP domain superfamily is divided into several functional sub-groups based on their diverse functions and mechanisms:[4][7]
- Class I aminoacyl-tRNA synthetases (AATRSs): These enzymes are responsible for attaching amino acids to their corresponding tRNAs
- Nucleotide synthetases: This group includes enzymes involved in the biosynthesis of nucleotides, such as GMP synthetase (GMPS) and NAD synthetase (NADS)
- Asparagine synthetase (ASNS): An enzyme that catalyses the synthesis of asparagine from aspartate and glutamine
- ATP sulfurylases: These enzymes catalyse the first step in sulfate assimilation and activation
- Electron transfer flavoprotein α (ETFα): A non-enzymatic protein involved in electron transfer processes
- Cryptochrome/DNA photolyase family: These proteins are involved in DNA repair and light-dependent signalling
- Other adenylating enzymes: This group includes various enzymes that catalyse adenylation reactions
Evolution
[edit]Despite sharing structural similarities with Rossmann folds, the HUP domain appears to have evolved independently. The HUP domain has demonstrated remarkable evolutionary plasticity with an evolution characterised by structural and functional diversification while maintaining a conserved core structure. Ribose binding remains conserved, but the location and mode of binding to the base and phosphate moieties of nucleotides have diverged over time.[3]
References
[edit]- ^ Newberry, Kate J; Hou, Ya-Ming; Perona, John J (2002-06-01). "Structural origins of amino acid selection without editing by cysteinyl-tRNA synthetase". The EMBO Journal. 21 (11): 2778–2787. doi:10.1093/emboj/21.11.2778. ISSN 1460-2075. PMC 126036. PMID 12032090.
- ^ Aravind, L.; Anantharaman, Vivek; Koonin, Eugene V. (2002-07-01). "Monophyly of class I aminoacyl tRNA synthetase, USPA, ETFP, photolyase, and PP-ATPase nucleotide-binding domains: implications for protein evolution in the RNA". Proteins. 48 (1): 1–14. doi:10.1002/prot.10064. ISSN 1097-0134. PMID 12012333.
- ^ a b c Gruic-Sovulj, Ita; Longo, Liam M; Jabłońska, Jagoda; Tawfik, Dan S (2022-02-01). "The evolutionary history of the HUP domain". Critical Reviews in Biochemistry and Molecular Biology. 57 (1): 1–15. doi:10.1080/10409238.2021.1957764. ISSN 1549-7798. PMID 34384295.
- ^ a b c d Dessailly, Benoit H.; Redfern, Oliver C.; Cuff, Alison L.; Orengo, Christine A. (2010-11-10). "Detailed analysis of function divergence in a large and diverse domain superfamily: toward a refined protocol of function classification". Structure. 18 (11): 1522–1535. doi:10.1016/j.str.2010.08.017. ISSN 1878-4186. PMC 3023962. PMID 21070951.
- ^ Gruic-Sovulj, Ita; Longo, Liam M.; Jabłońska, Jagoda; Tawfik, Dan S. (February 2022). "The evolutionary history of the HUP domain". Critical Reviews in Biochemistry and Molecular Biology. 57 (1): 1–15. doi:10.1080/10409238.2021.1957764. ISSN 1549-7798. PMID 34384295.
- ^ Dessailly, Benoit H.; Orengo, Christine (2013), "Functional Diversity of the HUP Domain Superfamily", Protein Families, John Wiley & Sons, Ltd, pp. 159–189, doi:10.1002/9781118743089.ch7, ISBN 978-1-118-74308-9, retrieved 2025-03-27
- ^ Waman, Vaishali P.; Yin, Jialin; Sen, Neeladri; Firdaus-Raih, Mohd; Lam, Su Datt; Orengo, Christine (2023-10-16), Understanding structural and functional diversity of ATP-PPases using protein domains and functional families in CATH database, bioRxiv, doi:10.1101/2023.10.12.562014, retrieved 2025-03-27