Protein Family Models

This entry represents the alpha helical (AH) and Ribosome-InterSubunit (RIS) domains found in RelA/SpoT proteins, adjacent to the ACT domain [1,2]. AH domain interacts with A/R tRNA and links the very C-terminal subdomains with TGS domain. The RIS domain is part of the binding interface between the C-terminal region and the ribosome, bridging the large and the small ribosomal subunits. RIS contains a four-stranded beta-sheet and a short alpha-helix. RelA/SpoT-homologue proteins (RHS) mediate the stringent response in bacteria which enables its metabolic adaptation under stress conditions. These enzymes synthesise the second messenger (p)ppGpp, which is a regulatory metabolite of the stringent response characterised by growth arrest and the modulation of gene expression in response to various nutritional stresses [1-3]. [1]. 27434674. Ribosome*RelA structures reveal the mechanism of stringent response activation. Loveland AB, Bah E, Madireddy R, Zhang Y, Brilot AF, Grigorieff N, Korostelev AA;. Elife. 2016; [Epub ahead of print]. [2]. 32937119. Structural Basis for Regulation of the Opposing (p)ppGpp Synthetase and Hydrolase within the Stringent Response Orchestrator Rel. Pausch P, Abdelshahid M, Steinchen W, Schafer H, Gratani FL, Freibert SA, Wolz C, Turgay K, Wilson DN, Bange G;. Cell Rep. 2020;32:108157. [3]. 15866041. ppGpp: a global regulator in Escherichia coli. Magnusson LU, Farewell A, Nystrom T;. Trends Microbiol. 2005;13:236-242. (from Pfam)

Date:

2024-10-16

ACT domains bind to amino acids and regulate associated enzyme domains. These ACT domains are found at the C-terminus of the RelA protein. (from Pfam)

Date:

2024-08-14

HD domains are metal dependent phosphohydrolases. [1]. 9868367. The HD domain defines a new superfamily of metal-dependent phosphohydrolases. Aravind L, Koonin EV;. Trends Biochem Sci 1998;23:469-472. (from Pfam)

Date:

2024-10-16

This region of unknown function is found in RelA and SpoT of Escherichia coli, and their homologues in plants and in other eubacteria. RelA is a guanosine 3',5'-bis-pyrophosphate (ppGpp) synthetase (EC:2.7.6.5) while SpoT is thought to be a bifunctional enzyme catalysing both ppGpp synthesis and degradation (ppGpp 3'-pyrophosphohydrolase, (EC:3.1.7.2)) [1]. This region is often found in association with HD (Pfam:PF01966), a metal-dependent phosphohydrolase, TGS (Pfam:PF02824) which is a possible nucleotide-binding region, and the ACT regulatory domain (Pfam:PF01842). [1]. 2005134. Residual guanosine 3',5'-bispyrophosphate synthetic activity of relA null mutants can be eliminated by spoT null mutations. Xiao H, Kalman M, Ikehara K, Zemel S, Glaser G, Cashel M;. J Biol Chem 1991;266:5980-5990. (from Pfam)

Date:

2024-10-16

The TGS domain is named after ThrRS, GTPase, and SpoT [1]. Interestingly, TGS domain was detected also at the amino terminus of the uridine kinase from the spirochaete Treponema pallidum (but not any other organism, including the related spirochaete Borrelia burgdorferi). TGS is a small domain that consists of ~50 amino acid residues and is predicted to possess a predominantly beta-sheet structure. There is no direct information on the functions of the TGS domain, but its presence in two types of regulatory proteins (the GTPases and guanosine polyphosphate phosphohydrolases/synthetases) suggests a ligand (most likely nucleotide)-binding, regulatory role [1]. [1]. 10447505. Evolution of aminoacyl-tRNA synthetases--analysis of unique domain architectures and phylogenetic trees reveals a complex history of horizontal gene transfer events. Wolf YI, Aravind L, Grishin NV, Koonin EV;. Genome Res 1999;9:689-710. [2]. 10319817. The structure of threonyl-tRNA synthetase-tRNA(Thr) complex enlightens its repressor activity and reveals an essential zinc ion in the active site. Sankaranarayanan R, Dock-Bregeon AC, Romby P, Caillet J, Springer M, Rees B, Ehresmann C, Ehresmann B, Moras D;. Cell 1999;97:371-381. (from Pfam)

Date:

2024-10-16

HD domains are metal dependent phosphohydrolases. [1]. 9868367. The HD domain defines a new superfamily of metal-dependent phosphohydrolases. Aravind L, Koonin EV;. Trends Biochem Sci 1998;23:469-472. (from Pfam)

Date:

2024-10-16

RelA/SpoT family protein is involved in guanosine tetraphosphate metabolic process, such as GTP pyrophosphokinase that catalyzes the formation of pppGpp which is then hydrolyzed to form ppGpp; contains HD, nucleotidyltransferase (NT), TGS, alpha helical (AH), Ribosome-InterSubunit (RIS) and ACT domains

Date:

2024-07-08

The functions of E. coli RelA and SpoT differ somewhat. RelA (EC 2.7.6.5) produces pppGpp (or ppGpp) from ATP and GTP (or GDP). SpoT (EC 3.1.7.2) degrades ppGpp, but may also act as a secondary ppGpp synthetase. The two proteins are strongly similar. In many species, a single homolog to SpoT and RelA appears reponsible for both ppGpp synthesis and ppGpp degradation. (p)ppGpp is a regulatory metabolite of the stringent response, but appears also to be involved in antibiotic biosynthesis in some species.

Date:

2024-06-27