Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 24 (5), 874-82

Superdomains in the Protein Structure Hierarchy: The Case of PTP-C2

Affiliations

Superdomains in the Protein Structure Hierarchy: The Case of PTP-C2

Donald T Haynie et al. Protein Sci.

Abstract

Superdomain is uniquely defined in this work as a conserved combination of different globular domains in different proteins. The amino acid sequences of 25 structurally and functionally diverse proteins from fungi, plants, and animals have been analyzed in a test of the superdomain hypothesis. Each of the proteins contains a protein tyrosine phosphatase (PTP) domain followed by a C2 domain. Four novel conserved sequence motifs have been identified, one in the PTP domain and three in the C2 domain. All contribute to the PTP-C2 domain interface in PTEN, a tumor suppressor, and all are more conserved than the PTP signature motif, HCX3 (K/R)XR, in the 25 sequences. We show that PTP-C2 was formed prior to the fungi, plant, and animal kingdom divergence. A superdomain as defined here does not fit the usual protein structure classification system. The demonstrated existence of one superdomain suggests the existence of others.

Keywords: domain; evolution; hierarchy; protein; structure; superdomain.

Figures

Figure 1
Figure 1
Excerpts of PTP-C2 amino acid sequence alignment. A) Phosphatase signature motif. B) Motif 1, PS(Q/H)(K/R)RYΦXYF. C) Motif 2, Φ2GDΦ3(R/K)ΦYH. D) Motif 3, ΦFXΦQFHTΦ2. E) Motif 4, KX(D/E)L(D/E)X5(R/K). Green, aromatic residues. Magenta, acidic residues. Cyan, basic residues. Gold, glycine. Yellow, others. Gray, no alignment.
Figure 2
Figure 2
Location in PTEN of the PTP-C2 superdomain conserved motifs. The PTP domain is at the top in each case, the C2 domain at the bottom. A) Motif 1, PS(Q/H)(K/R)RYΦXYF. B) Motif 2, Φ2GDΦ3(R/K)ΦYH. C) Motif 3, ΦFXΦQFHTΦ2. D) Motif 4, KX(D/E)L(D/E)X5(R/K). All atoms of each residue in each motif are shown space-filled and colored orange. The 1D5R structure was utilized for visualization.
Figure 3
Figure 3
Calculated isoelectric point versus nominal percentage identity for the present PTP-C2 superdomain sequences. The comparisons were made with respect to human TNS3. A cyan background represents basicity, and a rose background, acidity. Data points for the two plant proteins are shown as red squares, aquatic organisms as green triangles, and human PTEN as a blue star. An arrow highlights the leech protein.
Figure 4
Figure 4
Molecular architecture of PTP-C2 superdomain proteins. Domain composition is diverse. Green, PTP-C2. Red, SH2. Yellow, PTB. Olive, cysteine-rich Zn2+-binding. Violet, karyopherin β, comprising armadillo/β-catenin-like repeats. Orange, Ser/Thr kinase. Blue, DNA J. The scale bar represents amino acid residues.
Figure 5
Figure 5
PTP-C2 superdomain phylogenetic trees. All sequences of this work were included in comparisons to human TNS3 PTP, C2 or PTP-C2. Human TNS1, orange. Human TNS2, cyan. Human PTEN, violet. The two fungal proteins, red. The two plant proteins, green. Each comparison is quantified by a percentage of the bootstrap consensus tree. The higher the number, the higher the reliability of the branch. See Materials and Methods section for the list of proteins analyzed and a description of the procedure. Supporting Information Table S2 presents details of the proteins included in the comparison. The text of Supporting Information contains further details of the comparison.

Similar articles

See all similar articles

Cited by 3 PubMed Central articles

Feedback