Limits...
Multiple domain insertions and losses in the evolution of the Rab prenylation complex.

Rasteiro R, Pereira-Leal JB - BMC Evol. Biol. (2007)

Bottom Line: REP).We identified the orthologues of the components of the Rab prenylation machinery in 43 organisms, representing the crown eukaryotic groups.We characterize in detail the domain structure of all these components and the phylogenetic relationships between the individual domains.

View Article: PubMed Central - HTML - PubMed

Affiliation: Instituto Gulbenkian de Ciência, Apartado 14, P-2781-901 Oeiras, Portugal. rrasteiro@igc.gulbenkian.pt

ABSTRACT

Background: Rab proteins are regulators of vesicular trafficking, requiring a lipid modification for proper function, prenylation of C-terminal cysteines. This is catalysed by a complex of a catalytic heterodimer (Rab Geranylgeranyl Transferase - RabGGTase) and an accessory protein (Rab Escort Protein. REP). Components of this complex display domain insertions relative to paralogous proteins. The function of these inserted domains is unclear.

Results: We profiled the domain architecture of the components of the Rab prenylation complex in evolution. We identified the orthologues of the components of the Rab prenylation machinery in 43 organisms, representing the crown eukaryotic groups. We characterize in detail the domain structure of all these components and the phylogenetic relationships between the individual domains.

Conclusion: We found different domain insertions in different taxa, in alpha-subunits of RGGTase and REP. Our results suggest that there were multiple insertions, expansions and contractions in the evolution of this prenylation complex.

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Related in: MedlinePlus

(A) scheme illustrating the location of the sequence conserved regions (SCRs) in RabGDI and REP sequences, as well as the variable size of the region between SCR1A and SCR2. The broken yellow and blue boxes indicate the "gap" in the alignment of these sequences with mammalian REP. Adapted from [13] (B) Neighbor-Joining tree of selected sequences of REP and RabGDI, illustrating that classification of these sequences into one of the two subfamilies is clear. The same tree with bootstrap vaues is provided as supplementary Figure S6. Species codes are Aaeg – Aedes aegypti; Afum – Aspergillus fumigatus; Agam – Anopheles gambiae; Atha – Arabidopsis thaliana; Cbri – Caenorhabditis briggsae; Cele-Caenorhabditis elegans; Cint – Ciona intestinalis; Cmer – Cyanidioschyzon merolae; Cneo – Cryptococcus neoformans; Cpar – Cryptosporodium parvum; Crei-Chlamydomonas reinhardtii; Ddis – Dictyostelium discoideum; Dmel – Drosophila melanogaster; Dpse – Drosophila pseudoobscura; Drer – Danio rerio; Gint-Giardis intestinalis; Hsap – Homo sapiens; Mbre – Monosiga brevicollis; Mmus-Mus musculus; Ngru – Naegleria gruberi; Nvec – Nematostella vectensis; Osat-Oryza sativa; Otau – Ostreococcus tauri; Pber – Plasmodium berghei; Pfal – Plasmodium falciparum; Ppyg-Pongo pygmaeus; Pram – Phytophthora ramorum; Psoj – Phytophthora sojae; Ptri-Populus trichocarpa; Pyoe – Plamodium yoelii; Rnor – Rattus norvegicus; Scer-Saccharomyces cerevisae; Sjap – Schistosoma japonicum; Spom-Schizosaccharomyces pombe; Tbru – Trypanosoma brucei; Tcas – Tribolium castaneum; Tcru – Trypanosoma cruzi; Tpse-Thalassiosira pseudonana; Tnig – Tetraodon nigroviridis; Trub – Takifugu rubripes; Tthe – Tetrahymena thermophila; Xlae – Xenopus laevis; Xtro – Xenopus tropicalis; Ylip – Yarrowia lipolytica (C) Plot of the size of the region between SCR1A and SCR2 in the different species, measured in number of amino acids. The bars are coded according to the colors used in Figure 2 and same color denotes identifiable sequence similarity. The blue and pink dotted perpendicular lines are for reference and indicate the number of amino acids between SCR1B and SCR2 for RabGDI and MRS6, respectively. A red D indicates that the insert contains a predicted disordered region [51], whereas a cross means that such regions are not predicted in the insert.
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Figure 4: (A) scheme illustrating the location of the sequence conserved regions (SCRs) in RabGDI and REP sequences, as well as the variable size of the region between SCR1A and SCR2. The broken yellow and blue boxes indicate the "gap" in the alignment of these sequences with mammalian REP. Adapted from [13] (B) Neighbor-Joining tree of selected sequences of REP and RabGDI, illustrating that classification of these sequences into one of the two subfamilies is clear. The same tree with bootstrap vaues is provided as supplementary Figure S6. Species codes are Aaeg – Aedes aegypti; Afum – Aspergillus fumigatus; Agam – Anopheles gambiae; Atha – Arabidopsis thaliana; Cbri – Caenorhabditis briggsae; Cele-Caenorhabditis elegans; Cint – Ciona intestinalis; Cmer – Cyanidioschyzon merolae; Cneo – Cryptococcus neoformans; Cpar – Cryptosporodium parvum; Crei-Chlamydomonas reinhardtii; Ddis – Dictyostelium discoideum; Dmel – Drosophila melanogaster; Dpse – Drosophila pseudoobscura; Drer – Danio rerio; Gint-Giardis intestinalis; Hsap – Homo sapiens; Mbre – Monosiga brevicollis; Mmus-Mus musculus; Ngru – Naegleria gruberi; Nvec – Nematostella vectensis; Osat-Oryza sativa; Otau – Ostreococcus tauri; Pber – Plasmodium berghei; Pfal – Plasmodium falciparum; Ppyg-Pongo pygmaeus; Pram – Phytophthora ramorum; Psoj – Phytophthora sojae; Ptri-Populus trichocarpa; Pyoe – Plamodium yoelii; Rnor – Rattus norvegicus; Scer-Saccharomyces cerevisae; Sjap – Schistosoma japonicum; Spom-Schizosaccharomyces pombe; Tbru – Trypanosoma brucei; Tcas – Tribolium castaneum; Tcru – Trypanosoma cruzi; Tpse-Thalassiosira pseudonana; Tnig – Tetraodon nigroviridis; Trub – Takifugu rubripes; Tthe – Tetrahymena thermophila; Xlae – Xenopus laevis; Xtro – Xenopus tropicalis; Ylip – Yarrowia lipolytica (C) Plot of the size of the region between SCR1A and SCR2 in the different species, measured in number of amino acids. The bars are coded according to the colors used in Figure 2 and same color denotes identifiable sequence similarity. The blue and pink dotted perpendicular lines are for reference and indicate the number of amino acids between SCR1B and SCR2 for RabGDI and MRS6, respectively. A red D indicates that the insert contains a predicted disordered region [51], whereas a cross means that such regions are not predicted in the insert.

Mentions: Rab escort proteins (REP) belong to the same protein family as Rab GDP dissociation inhibitors (RabGDI). They are both classified in the SCOP hierarchy [31] as FAD/NAD(P)-binding domain fold and superfamily, which suggests a common ancestry. Their structure comprises two domains: domain I include the Rab binding platform, whereas domain II in REP mediates binding to the alpha-subunit of RGGTase [29,45]. REP and RabGDI share conserved regions, termed SCRs (sequence conserved regions), which are highlighted in Figure 4 as brown boxes. Multiple sequence alignments of REPs and RabGDI reveal that mammalian REPs display an insertion between domain I and domain II, absent in RabGDI, which maps roughly to a sequence region delimited by the conserved regions SCR1B and SCR2 [13,45]. This insert appears to be larger in vertebrate sequences than in S. cerevisae [13]. The function of this insert is unclear, particularly at the light of the recent structure of REP1 in complex with RGGT, which shows that it is not involved in contacts with the RGGTase subunits nor with Rab substrates [29].


Multiple domain insertions and losses in the evolution of the Rab prenylation complex.

Rasteiro R, Pereira-Leal JB - BMC Evol. Biol. (2007)

(A) scheme illustrating the location of the sequence conserved regions (SCRs) in RabGDI and REP sequences, as well as the variable size of the region between SCR1A and SCR2. The broken yellow and blue boxes indicate the "gap" in the alignment of these sequences with mammalian REP. Adapted from [13] (B) Neighbor-Joining tree of selected sequences of REP and RabGDI, illustrating that classification of these sequences into one of the two subfamilies is clear. The same tree with bootstrap vaues is provided as supplementary Figure S6. Species codes are Aaeg – Aedes aegypti; Afum – Aspergillus fumigatus; Agam – Anopheles gambiae; Atha – Arabidopsis thaliana; Cbri – Caenorhabditis briggsae; Cele-Caenorhabditis elegans; Cint – Ciona intestinalis; Cmer – Cyanidioschyzon merolae; Cneo – Cryptococcus neoformans; Cpar – Cryptosporodium parvum; Crei-Chlamydomonas reinhardtii; Ddis – Dictyostelium discoideum; Dmel – Drosophila melanogaster; Dpse – Drosophila pseudoobscura; Drer – Danio rerio; Gint-Giardis intestinalis; Hsap – Homo sapiens; Mbre – Monosiga brevicollis; Mmus-Mus musculus; Ngru – Naegleria gruberi; Nvec – Nematostella vectensis; Osat-Oryza sativa; Otau – Ostreococcus tauri; Pber – Plasmodium berghei; Pfal – Plasmodium falciparum; Ppyg-Pongo pygmaeus; Pram – Phytophthora ramorum; Psoj – Phytophthora sojae; Ptri-Populus trichocarpa; Pyoe – Plamodium yoelii; Rnor – Rattus norvegicus; Scer-Saccharomyces cerevisae; Sjap – Schistosoma japonicum; Spom-Schizosaccharomyces pombe; Tbru – Trypanosoma brucei; Tcas – Tribolium castaneum; Tcru – Trypanosoma cruzi; Tpse-Thalassiosira pseudonana; Tnig – Tetraodon nigroviridis; Trub – Takifugu rubripes; Tthe – Tetrahymena thermophila; Xlae – Xenopus laevis; Xtro – Xenopus tropicalis; Ylip – Yarrowia lipolytica (C) Plot of the size of the region between SCR1A and SCR2 in the different species, measured in number of amino acids. The bars are coded according to the colors used in Figure 2 and same color denotes identifiable sequence similarity. The blue and pink dotted perpendicular lines are for reference and indicate the number of amino acids between SCR1B and SCR2 for RabGDI and MRS6, respectively. A red D indicates that the insert contains a predicted disordered region [51], whereas a cross means that such regions are not predicted in the insert.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1994686&req=5

Figure 4: (A) scheme illustrating the location of the sequence conserved regions (SCRs) in RabGDI and REP sequences, as well as the variable size of the region between SCR1A and SCR2. The broken yellow and blue boxes indicate the "gap" in the alignment of these sequences with mammalian REP. Adapted from [13] (B) Neighbor-Joining tree of selected sequences of REP and RabGDI, illustrating that classification of these sequences into one of the two subfamilies is clear. The same tree with bootstrap vaues is provided as supplementary Figure S6. Species codes are Aaeg – Aedes aegypti; Afum – Aspergillus fumigatus; Agam – Anopheles gambiae; Atha – Arabidopsis thaliana; Cbri – Caenorhabditis briggsae; Cele-Caenorhabditis elegans; Cint – Ciona intestinalis; Cmer – Cyanidioschyzon merolae; Cneo – Cryptococcus neoformans; Cpar – Cryptosporodium parvum; Crei-Chlamydomonas reinhardtii; Ddis – Dictyostelium discoideum; Dmel – Drosophila melanogaster; Dpse – Drosophila pseudoobscura; Drer – Danio rerio; Gint-Giardis intestinalis; Hsap – Homo sapiens; Mbre – Monosiga brevicollis; Mmus-Mus musculus; Ngru – Naegleria gruberi; Nvec – Nematostella vectensis; Osat-Oryza sativa; Otau – Ostreococcus tauri; Pber – Plasmodium berghei; Pfal – Plasmodium falciparum; Ppyg-Pongo pygmaeus; Pram – Phytophthora ramorum; Psoj – Phytophthora sojae; Ptri-Populus trichocarpa; Pyoe – Plamodium yoelii; Rnor – Rattus norvegicus; Scer-Saccharomyces cerevisae; Sjap – Schistosoma japonicum; Spom-Schizosaccharomyces pombe; Tbru – Trypanosoma brucei; Tcas – Tribolium castaneum; Tcru – Trypanosoma cruzi; Tpse-Thalassiosira pseudonana; Tnig – Tetraodon nigroviridis; Trub – Takifugu rubripes; Tthe – Tetrahymena thermophila; Xlae – Xenopus laevis; Xtro – Xenopus tropicalis; Ylip – Yarrowia lipolytica (C) Plot of the size of the region between SCR1A and SCR2 in the different species, measured in number of amino acids. The bars are coded according to the colors used in Figure 2 and same color denotes identifiable sequence similarity. The blue and pink dotted perpendicular lines are for reference and indicate the number of amino acids between SCR1B and SCR2 for RabGDI and MRS6, respectively. A red D indicates that the insert contains a predicted disordered region [51], whereas a cross means that such regions are not predicted in the insert.
Mentions: Rab escort proteins (REP) belong to the same protein family as Rab GDP dissociation inhibitors (RabGDI). They are both classified in the SCOP hierarchy [31] as FAD/NAD(P)-binding domain fold and superfamily, which suggests a common ancestry. Their structure comprises two domains: domain I include the Rab binding platform, whereas domain II in REP mediates binding to the alpha-subunit of RGGTase [29,45]. REP and RabGDI share conserved regions, termed SCRs (sequence conserved regions), which are highlighted in Figure 4 as brown boxes. Multiple sequence alignments of REPs and RabGDI reveal that mammalian REPs display an insertion between domain I and domain II, absent in RabGDI, which maps roughly to a sequence region delimited by the conserved regions SCR1B and SCR2 [13,45]. This insert appears to be larger in vertebrate sequences than in S. cerevisae [13]. The function of this insert is unclear, particularly at the light of the recent structure of REP1 in complex with RGGT, which shows that it is not involved in contacts with the RGGTase subunits nor with Rab substrates [29].

Bottom Line: REP).We identified the orthologues of the components of the Rab prenylation machinery in 43 organisms, representing the crown eukaryotic groups.We characterize in detail the domain structure of all these components and the phylogenetic relationships between the individual domains.

View Article: PubMed Central - HTML - PubMed

Affiliation: Instituto Gulbenkian de Ciência, Apartado 14, P-2781-901 Oeiras, Portugal. rrasteiro@igc.gulbenkian.pt

ABSTRACT

Background: Rab proteins are regulators of vesicular trafficking, requiring a lipid modification for proper function, prenylation of C-terminal cysteines. This is catalysed by a complex of a catalytic heterodimer (Rab Geranylgeranyl Transferase - RabGGTase) and an accessory protein (Rab Escort Protein. REP). Components of this complex display domain insertions relative to paralogous proteins. The function of these inserted domains is unclear.

Results: We profiled the domain architecture of the components of the Rab prenylation complex in evolution. We identified the orthologues of the components of the Rab prenylation machinery in 43 organisms, representing the crown eukaryotic groups. We characterize in detail the domain structure of all these components and the phylogenetic relationships between the individual domains.

Conclusion: We found different domain insertions in different taxa, in alpha-subunits of RGGTase and REP. Our results suggest that there were multiple insertions, expansions and contractions in the evolution of this prenylation complex.

Show MeSH
Related in: MedlinePlus