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The PAM domain, a multi-protein complex-associated module with an all-alpha-helix fold.

Ciccarelli FD, Izaurralde E, Bork P - BMC Bioinformatics (2003)

Bottom Line: We identified a new module, the PAM domain (PCI/PINT associated module), present in single subunits of well characterized multiprotein complexes, like the regulatory lid of the 26S proteasome, the COP-9 signalosome and the Sac3-Thp1 complex.This module is an around 200 residue long domain with a predicted TPR-like all-alpha-helical fold.The occurrence of the PAM domain in specific subunits of multimeric protein complexes, together with the role of other all-alpha-helical folds in protein-protein interactions, suggest a function for this domain in mediating transient binding to diverse target proteins.

View Article: PubMed Central - HTML - PubMed

Affiliation: European Molecular Biology Laboratory, Meyerhofstr, 1, 69012 Heidelberg, Germany. francesca.ciccarelli@embl.de

ABSTRACT

Background: Multimeric protein complexes have a role in many cellular pathways and are highly interconnected with various other proteins. The characterization of their domain composition and organization provides useful information on the specific role of each region of their sequence.

Results: We identified a new module, the PAM domain (PCI/PINT associated module), present in single subunits of well characterized multiprotein complexes, like the regulatory lid of the 26S proteasome, the COP-9 signalosome and the Sac3-Thp1 complex. This module is an around 200 residue long domain with a predicted TPR-like all-alpha-helical fold.

Conclusions: The occurrence of the PAM domain in specific subunits of multimeric protein complexes, together with the role of other all-alpha-helical folds in protein-protein interactions, suggest a function for this domain in mediating transient binding to diverse target proteins.

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Phylogenetic tree and domain architecture of the protein families bearing the PAM domain. The tree was built using the corresponding PAM domain region of the CSN2, Rpn3, Thp1 proteins in representative species. Where uncharacterized, the proteins are indicated with their database accession number. The nodes with a bootstrap support exceeding 90% are indicated with coloured lines, those with a bootstrap value below 90% are reported in black. The domain architecture was derived from the SMART database [28]. A divergent version of the PCI/PINT domain is indicated in yellow (Table 1, see Additional data). It should be noted that the N. crassa EAA35198 protein is a hypothetical protein derived from gene prediction. As it is the only protein with a PAM domain showing the thiolase domains, it could be that the gene prediction is wrong and the actual protein is bearing only the PAM domain. Abbreviations: PINT: Proteasome, Int-6, Nip-1 and TRIP-15; PAM, PCI/PINT associated module; Thiolase: Thiolase, N-terminal domain; Thiolase_C: Thiolase, C-terminal domain.
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Figure 2: Phylogenetic tree and domain architecture of the protein families bearing the PAM domain. The tree was built using the corresponding PAM domain region of the CSN2, Rpn3, Thp1 proteins in representative species. Where uncharacterized, the proteins are indicated with their database accession number. The nodes with a bootstrap support exceeding 90% are indicated with coloured lines, those with a bootstrap value below 90% are reported in black. The domain architecture was derived from the SMART database [28]. A divergent version of the PCI/PINT domain is indicated in yellow (Table 1, see Additional data). It should be noted that the N. crassa EAA35198 protein is a hypothetical protein derived from gene prediction. As it is the only protein with a PAM domain showing the thiolase domains, it could be that the gene prediction is wrong and the actual protein is bearing only the PAM domain. Abbreviations: PINT: Proteasome, Int-6, Nip-1 and TRIP-15; PAM, PCI/PINT associated module; Thiolase: Thiolase, N-terminal domain; Thiolase_C: Thiolase, C-terminal domain.

Mentions: Multiple sequence alignment of representative proteins containing the PAM domain. Of the original set, only sequences with less than 80% identity to each other are shown. The borders of the domain have been assigned taking into account the results of the sequence alignments from PSI-BLAST [17] and the structural alignments from 3D-Jury [23]. Sequences are grouped by phylogenetic relationships, as explained in the legend to Fig. 2. For each sequence, the species, the domain starting and ending residues and the database accession number are reported. The consensus in 70% of the sequences is below the alignment; h, l, p and + indicate hydrophobic, aliphatic, polar, and positive residues, respectively. Hydrophobic residues are highlighted in blue, aliphatic residues in cyan, polar residues in green, positive residues in red and other conserved residues in yellow. The secondary structure predictions using PHD [24], PsiPred [25] and SAM-T99 [26] are reported. For PHD, the upper cases indicate elements predicted with expected average accuracy >82%, and lower cases those predicted with expected average accuracy <82%. The consensus among the three methods is indicated in red. The secondary structure elements of the Sec17 3D structure (1QQE) [27], taken as a representative of the TPR-like structural superfamily, are shown as red cylinders (α-helices: α5–α13). Abbreviations: Ag; Anopheles gambiae; At: Arabidopsis thaliana; Ce, Caenorhabditis elegans; Cs, Ciona savignyi; Dm, Drosophila melanogaster; Hs, Homo sapiens; Nc, Neurospora crassa; Nt: Nicotiana tabacum; Pf, Plasmodium falciparum; Py, Plasmodium yoelii; Sc, saccharomyces cerevisiae; Sp: Schizosaccharomices pombae; Tb, Trypanosoma brucei, Ec, Encephalitozoon cuniculi, H, helix.


The PAM domain, a multi-protein complex-associated module with an all-alpha-helix fold.

Ciccarelli FD, Izaurralde E, Bork P - BMC Bioinformatics (2003)

Phylogenetic tree and domain architecture of the protein families bearing the PAM domain. The tree was built using the corresponding PAM domain region of the CSN2, Rpn3, Thp1 proteins in representative species. Where uncharacterized, the proteins are indicated with their database accession number. The nodes with a bootstrap support exceeding 90% are indicated with coloured lines, those with a bootstrap value below 90% are reported in black. The domain architecture was derived from the SMART database [28]. A divergent version of the PCI/PINT domain is indicated in yellow (Table 1, see Additional data). It should be noted that the N. crassa EAA35198 protein is a hypothetical protein derived from gene prediction. As it is the only protein with a PAM domain showing the thiolase domains, it could be that the gene prediction is wrong and the actual protein is bearing only the PAM domain. Abbreviations: PINT: Proteasome, Int-6, Nip-1 and TRIP-15; PAM, PCI/PINT associated module; Thiolase: Thiolase, N-terminal domain; Thiolase_C: Thiolase, C-terminal domain.
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Related In: Results  -  Collection

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Figure 2: Phylogenetic tree and domain architecture of the protein families bearing the PAM domain. The tree was built using the corresponding PAM domain region of the CSN2, Rpn3, Thp1 proteins in representative species. Where uncharacterized, the proteins are indicated with their database accession number. The nodes with a bootstrap support exceeding 90% are indicated with coloured lines, those with a bootstrap value below 90% are reported in black. The domain architecture was derived from the SMART database [28]. A divergent version of the PCI/PINT domain is indicated in yellow (Table 1, see Additional data). It should be noted that the N. crassa EAA35198 protein is a hypothetical protein derived from gene prediction. As it is the only protein with a PAM domain showing the thiolase domains, it could be that the gene prediction is wrong and the actual protein is bearing only the PAM domain. Abbreviations: PINT: Proteasome, Int-6, Nip-1 and TRIP-15; PAM, PCI/PINT associated module; Thiolase: Thiolase, N-terminal domain; Thiolase_C: Thiolase, C-terminal domain.
Mentions: Multiple sequence alignment of representative proteins containing the PAM domain. Of the original set, only sequences with less than 80% identity to each other are shown. The borders of the domain have been assigned taking into account the results of the sequence alignments from PSI-BLAST [17] and the structural alignments from 3D-Jury [23]. Sequences are grouped by phylogenetic relationships, as explained in the legend to Fig. 2. For each sequence, the species, the domain starting and ending residues and the database accession number are reported. The consensus in 70% of the sequences is below the alignment; h, l, p and + indicate hydrophobic, aliphatic, polar, and positive residues, respectively. Hydrophobic residues are highlighted in blue, aliphatic residues in cyan, polar residues in green, positive residues in red and other conserved residues in yellow. The secondary structure predictions using PHD [24], PsiPred [25] and SAM-T99 [26] are reported. For PHD, the upper cases indicate elements predicted with expected average accuracy >82%, and lower cases those predicted with expected average accuracy <82%. The consensus among the three methods is indicated in red. The secondary structure elements of the Sec17 3D structure (1QQE) [27], taken as a representative of the TPR-like structural superfamily, are shown as red cylinders (α-helices: α5–α13). Abbreviations: Ag; Anopheles gambiae; At: Arabidopsis thaliana; Ce, Caenorhabditis elegans; Cs, Ciona savignyi; Dm, Drosophila melanogaster; Hs, Homo sapiens; Nc, Neurospora crassa; Nt: Nicotiana tabacum; Pf, Plasmodium falciparum; Py, Plasmodium yoelii; Sc, saccharomyces cerevisiae; Sp: Schizosaccharomices pombae; Tb, Trypanosoma brucei, Ec, Encephalitozoon cuniculi, H, helix.

Bottom Line: We identified a new module, the PAM domain (PCI/PINT associated module), present in single subunits of well characterized multiprotein complexes, like the regulatory lid of the 26S proteasome, the COP-9 signalosome and the Sac3-Thp1 complex.This module is an around 200 residue long domain with a predicted TPR-like all-alpha-helical fold.The occurrence of the PAM domain in specific subunits of multimeric protein complexes, together with the role of other all-alpha-helical folds in protein-protein interactions, suggest a function for this domain in mediating transient binding to diverse target proteins.

View Article: PubMed Central - HTML - PubMed

Affiliation: European Molecular Biology Laboratory, Meyerhofstr, 1, 69012 Heidelberg, Germany. francesca.ciccarelli@embl.de

ABSTRACT

Background: Multimeric protein complexes have a role in many cellular pathways and are highly interconnected with various other proteins. The characterization of their domain composition and organization provides useful information on the specific role of each region of their sequence.

Results: We identified a new module, the PAM domain (PCI/PINT associated module), present in single subunits of well characterized multiprotein complexes, like the regulatory lid of the 26S proteasome, the COP-9 signalosome and the Sac3-Thp1 complex. This module is an around 200 residue long domain with a predicted TPR-like all-alpha-helical fold.

Conclusions: The occurrence of the PAM domain in specific subunits of multimeric protein complexes, together with the role of other all-alpha-helical folds in protein-protein interactions, suggest a function for this domain in mediating transient binding to diverse target proteins.

Show MeSH