Abstract
BackgroundThe Hotdog fold was initially identified in the structure of Escherichia coli FabA and subsequently in 4-hydroxybenzoyl-CoA thioesterase from Pseudomonas sp. strain CBS. Since that time structural determinations have shown a number of other apparently unrelated proteins also share the Hotdog fold.ResultsUsing sequence analysis we unify a large superfamily of HotDog domains. Membership includes numerous prokaryotic, archaeal and eukaryotic proteins involved in several related, but distinct, catalytic activities, from metabolic roles such as thioester hydrolysis in fatty acid metabolism, to degradation of phenylacetic acid and the environmental pollutant 4-chlorobenzoate. The superfamily also includes FapR, a non-catalytic bacterial homologue that is involved in transcriptional regulation of fatty acid biosynthesis.We have defined 17 subfamilies, with some characterisation. Operon analysis has revealed numerous HotDog domain-containing proteins to be fusion proteins, where two genes, once separate but adjacent open-reading frames, have been fused into one open-reading frame to give a protein with two functional domains. Finally we have generated a Hidden Markov Model library from our analysis, which can be used as a tool for predicting the occurrence of HotDog domains in any protein sequence.ConclusionsThe HotDog domain is both an ancient and ubiquitous motif, with members found in the three branches of life.
Highlights
The Hotdog fold was initially identified in the structure of Escherichia coli FabA and subsequently in 4-hydroxybenzoyl-CoA thioesterase from Pseudomonas sp. strain CBS
We have found the HotDog domain, as we suggest calling the Hotdog fold, to be widespread in eukaryotes, bacteria, and archaea and to be involved in a range of cellular processes, from thioester hydrolysis, to phenylacetic acid degradation and transcriptional regulation of fatty acid biosynthesis
We have looked at gene context and operon structures and found many examples of fusion proteins, in which the HotDog domain has been fused to another protein to generate functional diversity
Summary
The Hotdog fold was initially identified in the structure of Escherichia coli FabA and subsequently in 4-hydroxybenzoyl-CoA thioesterase from Pseudomonas sp. strain CBS. The Hotdog fold was initially identified in the structure of Escherichia coli FabA and subsequently in 4-hydroxybenzoyl-CoA thioesterase from Pseudomonas sp. Noticed that each subunit of this dimeric enzyme contained a mixed α + β 'hot dog' fold [1] They described the seven-stranded antiparallel β-sheet as the 'bun', which wraps around a five-turn α-helical 'sausage', see Figure 1. This characteristic fold has been found in a number of other enzymes, including: 4-hydroxybenzoyl-CoA thioesterase (4HBT) from Pseudomonas sp. Each 171-residue subunit contains a Hotdog fold/ domain, consisting of a sevenstranded antiparallel b-sheet 'bun', coloured magenta and green, and a five-turn a-helical 'sausage' coloured blue and purple in the respective subunits.
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