- Discovery notes
- Open Access
The prokaryotic V4R domain is the likely ancestor of a key component of the eukaryotic vesicle transport system
© Podar et al; licensee BioMed Central Ltd. 2008
- Received: 17 January 2008
- Accepted: 25 January 2008
- Published: 25 January 2008
Intracellular vesicle traffic that enables delivery of proteins between the endoplasmic reticulum, Golgi and various endosomal subcompartments is one of the hallmarks of the eukaryotic cell. Its evolutionary history is not well understood but the process itself and the core vesicle traffic machinery are believed to be ancient. We show here that the 4-vinyl reductase (V4R) protein domain present in bacteria and archaea is homologous to the Bet3 subunit of the TRAPP1 vesicle-tethering complex that is conserved in all eukaryotes. This suggests, for the first time, a prokaryotic origin for one of the key eukaryotic trafficking proteins.
This article was reviewed by Gaspar Jekely and Mark A. Ragan
- Conserve Domain Database
- Last Eukaryotic Common Ancestor
- Bet3 Family
- Vesicle Traffic
The specificity of eukaryotic vesicle traffic is controlled by dozens of proteins and protein complexes that ensure correct docking, promote membrane fusion between vesicles, and target distinct compartments. Evolutionary analyses using genomic data from a wide range of eukaryotes indicate that the trafficking system is ancient and that most if not all the core constituents were present in the last eukaryotic common ancestor (LECA). However, no direct relationship has been so far detected between the eukaryotic proteins that are involved in vesicle traffic and any bacterial or archaeal proteins.
In the course of genome annotation and analysis for the hyperthermophilic crenarchaeon Ignicoccus hospitalis (Podar et al, manuscript in preparation), a significant sequence similarity was found between one of the several V4R proteins encoded in the genome (Ig1332) and the Bet3 family of proteins (pfam04051), which are constituents of the eukaryotic transport protein particle complex TRAPP1. The sequence similarity was detected using HMM analyses of Pfam domains present in the Ignicoccus proteome and RPS-BLAST searches with the Conserved Domains Database (CDD) at NCBI. A CDD search using the Ig1332 sequence as query retrieved TRAPP_Bet3 (pfam 04051) and COG1719 (V4R domain-containing orthologs) as equally strong (E-value = 0.03) and overlapping hits.
Proteins containing the V4R domain are encoded in the sequenced genomes of numerous bacteria and archaea, with a patchy distribution and without a strict link to any specific metabolic or taxonomic markers. Described as a predicted hydrocarbon-binding domain (COG1719) , V4R can be present either by itself or fused with other domains, primarily involved in transcription regulation and signal transduction. Limited experimental evidence connects V4R proteins to allosteric regulation of unrelated reactions that involve hydrophobic molecules in two species of bacteria [3, 4]. On the basis of these data, it is thought that V4R domains, in general, bind hydrophobic ligands and signal to effectors in cis or trans.
The overall architecture of Bet3 and V4R consists of five helices on one side and a twisted antiparallel four-stranded β-sheet on the other side. In the Bet3 family, two motifs, that have been previously described and are parts of helices α2 and α5, each contain a conserved pair of glycine residues separated by three amino acids (Figure 1). Based on the Bet3 and Tpc6 crystal structures, the glycine pairs allow tight packing of the α2–α5 helices at a distance incompatible with amino acids having a longer side chain. Notably, these two glycine doublets are conserved in most V4R domains as well, suggesting the existence of a similar, functionally important structural arrangement. Furthermore, around these glycines, additional conserved sequence features can be recognized between Bet3 and V4R (Figure 1B). These observations reinforce the conclusion that the Bet3 and V4R domains share a common origin and possess highly similar structural and, presumably, functional elements.
The functions of the V4R domain-containing proteins in archaea and bacteria are not thoroughly understood. Assuming that the primary role of this domain is in regulation and signaling , the recruitment of V4R for vesicular transport would have involved exaptation  during the buildup of the eukaryotic trafficking machinery at an early stage of eukaryogenesis. Alternatively, as V4R domains bind hydrophobic molecules, it cannot be ruled out that some of them are already involved in vesicular transport in prokaryotes. Vesicle formation is well known in some bacteria and archaea, although no evolutionary connection to the analogous eukaryotic process has been established . Interestingly, Ignicoccus hospitalis, which encodes seven V4R-containing proteins (an unusually large number of compared to any other archaeon), produces vesicles that migrate through a large periplasmic space and can fuse to the outer membrane or the cytoplasmic membrane via a still uncharacterized mechanism . If such a vesicle transport system exists in prokaryotes and employs the V4R domain, it could have been inherited by the LECA and subsequently underwent a major diversification at an early stage of eukaryotic evolution. Distinguishing this scenario from the exaptation hypothesis will depend on in-depth functional characterization of bacterial and archaeal V4R proteins, discovery of prokaryotic homologues to other eukaryotic vesicle transport machinery proteins, and further comparative analysis of vesicle transport systems in diverse eukaryotic lineages.
Gáspár Jékely: I read the paper and find it interesting and well written. I don't have any criticism.
Mark Ragan: The Golgi complex per se has been secondarily modified, sometimes substantially, in parasitic basal eukaryotes such as Giardia and Spironucleus (for a comprehensive recent review, see Sokolova et al., Cell and Tissue Biology 1(4):305–327, 2007). It could be interesting to explore, in somewhat more detail, the presence and interactions of the Bet3 subunit of the TRAPP1 complex in relation to the presence/absence, localisation and functions of other proteins involved in intracellular vesicle trafficking in these organisms.
My other comment relates to the discussion of a prokaryotic origin of V4R/Bet3. A broad (if patchy) distribution across prokaryotes does indeed suggest that the presence of V4R is ancestral among prokaryotes. This does not necessarily require, however, that LECA "inherited" one or more V4R homologs from a prokaryote, or that this homolog was already active in an ancient vesicle transport system in prokaryotes, as the final sentence of text indicates. The possibility is fascinating, but other options exist for moving V4R into the early eukaryotic lineage, including genome fusion and endosymbiotic transfer. Note that V4R could have been exaptive at that point within prokaryotes, as proposed for later within the eukaryote lineage.
MP is supported by the U.S. Department of Energy, Office of Science, Biological and Environmental Research programs at Oak Ridge National Laboratory (ORNL). ORNL is managed by UT-Battelle, LLC, for the U.S. Department of Energy under contract DE-AC05-00OR22725. KSM and EVK are supported by the Intramural Research Program of the National Institutes of Health, National Library of Medicine. M.P. acknowledges the support obtained from the Joint Genome Institute with the Ignicoccus hospitalis genome sequencing and analysis.
- Koumandou VL, Dacks JB, Coulson RM, Field MC: Control systems for membrane fusion in the ancestral eukaryote; evolution of tethering complexes and SM proteins. BMC Evol Biol. 2007, 7: 29-10.1186/1471-2148-7-29.PubMedPubMed CentralView ArticleGoogle Scholar
- Anantharaman V, Koonin EV, Aravind L: Regulatory potential, phyletic distribution and evolution of ancient, intracellular small-molecule-binding domains. J Mol Biol. 2001, 307: 1271-1292. 10.1006/jmbi.2001.4508.PubMedView ArticleGoogle Scholar
- Skarfstad E, O'Neill E, Garmendia J, Shingler V: Identification of an effector specificity subregion within the aromatic-responsive regulators DmpR and XylR by DNA shuffling. J Bacteriol. 2000, 182: 3008-3016. 10.1128/JB.182.11.3008-3016.2000.PubMedPubMed CentralView ArticleGoogle Scholar
- Suzuki JY, Bauer CE: A prokaryotic origin for light-dependent chlorophyll biosynthesis of plants. Proc Natl Acad Sci USA. 1995, 92: 3749-3753. 10.1073/pnas.92.9.3749.PubMedPubMed CentralView ArticleGoogle Scholar
- Kim YG, Raunser S, Munger C, Wagner J, Song YL, Cygler M, Walz T, Oh BH, Sacher M: The architecture of the multisubunit TRAPP I complex suggests a model for vesicle tethering. Cell. 2006, 127: 817-830. 10.1016/j.cell.2006.09.029.PubMedView ArticleGoogle Scholar
- Kim YG, Sohn EJ, Seo J, Lee KJ, Lee HS, Hwang I, Whiteway M, Sacher M, Oh BH: Crystal structure of bet3 reveals a novel mechanism for Golgi localization of tethering factor TRAPP. Nat Struct Mol Biol. 2005, 12: 38-45. 10.1038/nsmb871.PubMedView ArticleGoogle Scholar
- Kummel D, Muller JJ, Roske Y, Henke N, Heinemann U: Structure of the Bet3-Tpc6B core of TRAPP: two Tpc6 paralogs form trimeric complexes with Bet3 and Mum2. J Mol Biol. 2006, 361: 22-32. 10.1016/j.jmb.2006.06.012.PubMedView ArticleGoogle Scholar
- Kummel D, Muller JJ, Roske Y, Misselwitz R, Bussow K, Heinemann U: The structure of the TRAPP subunit TPC6 suggests a model for a TRAPP subcomplex. EMBO Rep. 2005, 6: 787-793. 10.1038/sj.embor.7400463.PubMedPubMed CentralView ArticleGoogle Scholar
- Huber H, Hohn MJ, Rachel R, Fuchs T, Wimmer VC, Stetter KO: A new phylum of Archaea represented by a nanosized hyperthermophilic symbiont. Nature. 2002, 417: 63-67. 10.1038/417063a.PubMedView ArticleGoogle Scholar
- Bennett-Lovsey RM, Herbert AD, Sternberg MJ, Kelley LA: Exploring the extremes of sequence/structure space with ensemble fold recognition in the program Phyre. Proteins. 2007, 70: 611-623. 10.1002/prot.21688.View ArticleGoogle Scholar
- Petrey D, Xiang Z, Tang CL, Xie L, Gimpelev M, Mitros T, Soto CS, Goldsmith-Fischman S, Kernytsky A, Schlessinger A, et al: Using multiple structure alignments, fast model building, and energetic analysis in fold recognition and homology modeling. Proteins. 2003, 53 (Suppl 6): 430-435. 10.1002/prot.10550.PubMedView ArticleGoogle Scholar
- Jones DT: Protein secondary structure prediction based on position-specific scoring matrices. J Mol Biol. 1999, 292: 195-202. 10.1006/jmbi.1999.3091.PubMedView ArticleGoogle Scholar
- Gibrat JF, Madej T, Bryant SH: Surprising similarities in structure comparison. Curr Opin Struct Biol. 1996, 6: 377-385. 10.1016/S0959-440X(96)80058-3.PubMedView ArticleGoogle Scholar
- Gould SJ, Vrba ES: Exaptation: A missing term in the science of form. Paleobiology. 1982, 8: 4-15.Google Scholar
- Mashburn-Warren LM, Whiteley M: Special delivery: vesicle trafficking in prokaryotes. Mol Microbiol. 2006, 61: 839-846. 10.1111/j.1365-2958.2006.05272.x.PubMedView ArticleGoogle Scholar
- Rachel R, Wyschkony I, Riehl S, Huber H: The ultrastructure of Ignicoccus: evidence for a novel outer membrane and for intracellular vesicle budding in an archaeon. Archaea. 2002, 1: 9-18.PubMedPubMed CentralView ArticleGoogle Scholar
- DeLano WL: The PyMOL Molecular Graphics System. 2002, [http://pymol.sourceforge.net/]Google Scholar
- Crooks GE, Hon G, Chandonia JM, Brenner SE: WebLogo: a sequence logo generator. Genome Res. 2004, 14: 1188-1190. 10.1101/gr.849004.PubMedPubMed CentralView ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.