ABSTRACT BLASTP searches with the CDS7 protein returned significant alignments to many proteins c... more ABSTRACT BLASTP searches with the CDS7 protein returned significant alignments to many proteins containing tandem immunoglobulin-like (Ig-like) domains. Domains I, II, and III each aligned to full or partial Ig-like domains from a diversity of molecules. These included vertebrate neurotrimin (e = 0.001, 28% identity), limbic-system associated membrane protein (e = 0.19, 27% identity), and opiod binding protein/cell adhesion molecule (e = 0.006, 29% identity), all of which are members of the IgLON family of neural cell adhesion molecules characterized GPI linkages and three tandem Ig-like domains (1). Alignments were also obtained to a wasp homolog of lachesin, a Drosophila cell-surface protein similar to the IgLON family. Searches against PFAM and the conserved domain database at NCBI with the sequences of each CDS7 domain returned hits to Ig-like domains with e-values ranging from 0.009 to 3.3. (Table S2). Since distant protein homologies are often better detected by methods sensitive to tertiary structure, we also used four protein structure prediction programs to evaluate domains I- III. A majority of these algorithms predicted Ig-like folds for domains I-III with strong statistical confidence (Table S2). In all of these searches, domain I was consistently most similar to V-set Ig-like domains, while domains II and III were most similar to I-set Ig- like domains. To further explore the similarity between CDS7 and members of the Ig superfamily, we constructed multiple sequence alignments between domains I-III and canonical V and I-set Ig-like domains. V and I-set Ig-like domains are characterized by a series of 8 beta-strands, labeled A, B, C, C', D, E, F, and G. V-set domains are longer than I-set domains due to a longer C' strand and an additional beta-strand (C") located between C' and D. Sequence profiles of V and I-set domains share a common set of frame residues, including a nearly invariant tryptophan in beta-strand C and a pair of cysteines forming a disulphide bridge between strands B and F (2, 3). We found domains I-III to match the common V/I-set frame residues at many positions, but that the conserved Trp was replaced by Met or Phe residues in domains I and III, respectively (Figure S4). Although the conserved cysteine residues were absent from all of the CDS7 domains, the disulphide bridge is not necessary for the fold (4) and several cysteines were replaced by small hydrophobic residues similar to those found in other Ig-like domains
ABSTRACT BLASTP searches with the CDS7 protein returned significant alignments to many proteins c... more ABSTRACT BLASTP searches with the CDS7 protein returned significant alignments to many proteins containing tandem immunoglobulin-like (Ig-like) domains. Domains I, II, and III each aligned to full or partial Ig-like domains from a diversity of molecules. These included vertebrate neurotrimin (e = 0.001, 28% identity), limbic-system associated membrane protein (e = 0.19, 27% identity), and opiod binding protein/cell adhesion molecule (e = 0.006, 29% identity), all of which are members of the IgLON family of neural cell adhesion molecules characterized GPI linkages and three tandem Ig-like domains (1). Alignments were also obtained to a wasp homolog of lachesin, a Drosophila cell-surface protein similar to the IgLON family. Searches against PFAM and the conserved domain database at NCBI with the sequences of each CDS7 domain returned hits to Ig-like domains with e-values ranging from 0.009 to 3.3. (Table S2). Since distant protein homologies are often better detected by methods sensitive to tertiary structure, we also used four protein structure prediction programs to evaluate domains I- III. A majority of these algorithms predicted Ig-like folds for domains I-III with strong statistical confidence (Table S2). In all of these searches, domain I was consistently most similar to V-set Ig-like domains, while domains II and III were most similar to I-set Ig- like domains. To further explore the similarity between CDS7 and members of the Ig superfamily, we constructed multiple sequence alignments between domains I-III and canonical V and I-set Ig-like domains. V and I-set Ig-like domains are characterized by a series of 8 beta-strands, labeled A, B, C, C', D, E, F, and G. V-set domains are longer than I-set domains due to a longer C' strand and an additional beta-strand (C") located between C' and D. Sequence profiles of V and I-set domains share a common set of frame residues, including a nearly invariant tryptophan in beta-strand C and a pair of cysteines forming a disulphide bridge between strands B and F (2, 3). We found domains I-III to match the common V/I-set frame residues at many positions, but that the conserved Trp was replaced by Met or Phe residues in domains I and III, respectively (Figure S4). Although the conserved cysteine residues were absent from all of the CDS7 domains, the disulphide bridge is not necessary for the fold (4) and several cysteines were replaced by small hydrophobic residues similar to those found in other Ig-like domains
Uploads
Papers by maria moreno