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Tryptogalinin is a tick Kunitz serine protease inhibitor with a unique intrinsic disorder.

Valdés JJ, Schwarz A, Cabeza de Vaca I, Calvo E, Pedra JH, Guallar V, Kotsyfakis M - PLoS ONE (2013)

Bottom Line: Using homology-based modeling (and other protein prediction programs) we were able to model and explain the multifaceted function of tryptogalinin.The N-terminus of the modeled tryptogalinin is detached from the rest of the peptide and exhibits intrinsic disorder allowing an increased flexibility for its high affinity with its inhibiting partners (i.e., serine proteases).By incorporating experimental and computational methods our data not only describes the function of a Kunitz peptide from Ixodes scapularis, but also allows us to hypothesize about the molecular basis of this function at the atomic level.

View Article: PubMed Central - PubMed

Affiliation: Institute of Parasitology, Biology Centre of the Academy of Sciences of the Czech Republic, České Budějovice, Czech Republic. valdjj@gmail.com

ABSTRACT

Background: A salivary proteome-transcriptome project on the hard tick Ixodes scapularis revealed that Kunitz peptides are the most abundant salivary proteins. Ticks use Kunitz peptides (among other salivary proteins) to combat host defense mechanisms and to obtain a blood meal. Most of these Kunitz peptides, however, remain functionally uncharacterized, thus limiting our knowledge about their biochemical interactions.

Results: We discovered an unusual cysteine motif in a Kunitz peptide. This peptide inhibits several serine proteases with high affinity and was named tryptogalinin due to its high affinity for β-tryptase. Compared with other functionally described peptides from the Acari subclass, we showed that tryptogalinin is phylogenetically related to a Kunitz peptide from Rhipicephalus appendiculatus, also reported to have a high affinity for β-tryptase. Using homology-based modeling (and other protein prediction programs) we were able to model and explain the multifaceted function of tryptogalinin. The N-terminus of the modeled tryptogalinin is detached from the rest of the peptide and exhibits intrinsic disorder allowing an increased flexibility for its high affinity with its inhibiting partners (i.e., serine proteases).

Conclusions: By incorporating experimental and computational methods our data not only describes the function of a Kunitz peptide from Ixodes scapularis, but also allows us to hypothesize about the molecular basis of this function at the atomic level.

Show MeSH
A multiple protein sequence alignment of the monolaris group from the I. scapularis sialome project [9].The multiple sequence alignment is based within the Cys framework showing the conserved Cys residues (black) and the arrow points to the oddly placed Cys position that depicts a potentially ‘atypical’ Cys motif in a monolaris protein described in the sialome of this tick – the asterisk denotes the missing Cys residue. All the monolaris sequences are named after their GenBank accession number and the ‘atypical’ sequence (DN971582) is shown last (at the bottom of the sequence alignment).
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pone-0062562-g001: A multiple protein sequence alignment of the monolaris group from the I. scapularis sialome project [9].The multiple sequence alignment is based within the Cys framework showing the conserved Cys residues (black) and the arrow points to the oddly placed Cys position that depicts a potentially ‘atypical’ Cys motif in a monolaris protein described in the sialome of this tick – the asterisk denotes the missing Cys residue. All the monolaris sequences are named after their GenBank accession number and the ‘atypical’ sequence (DN971582) is shown last (at the bottom of the sequence alignment).

Mentions: Based on our sequence alignment of the conserved Cys residues in Kunitz domain peptides, we identified in the sialome project of Ribeiro et al. [14] a modified Kunitz among all the described I. scapularis monolaris sequences. Specifically, one sequence (GenBank: DN971582, the last sequence in Figure 1) is missing the initial conserved Cys residue that forms the first disulfide bridge of archetypical Kunitz peptides (denoted with an asterisk in Figure 1). Figure 1 also shows this peptide possessing an oddly positioned Cys (indicated by an arrow) that does not follow any Kunitz Cys motif found in I. scapularis sialome or previously described in the literature [45]. The Cys motif that this Kunitz displays is: CX(8)CX(4)CX(7)CX(12)CX(3)C.


Tryptogalinin is a tick Kunitz serine protease inhibitor with a unique intrinsic disorder.

Valdés JJ, Schwarz A, Cabeza de Vaca I, Calvo E, Pedra JH, Guallar V, Kotsyfakis M - PLoS ONE (2013)

A multiple protein sequence alignment of the monolaris group from the I. scapularis sialome project [9].The multiple sequence alignment is based within the Cys framework showing the conserved Cys residues (black) and the arrow points to the oddly placed Cys position that depicts a potentially ‘atypical’ Cys motif in a monolaris protein described in the sialome of this tick – the asterisk denotes the missing Cys residue. All the monolaris sequences are named after their GenBank accession number and the ‘atypical’ sequence (DN971582) is shown last (at the bottom of the sequence alignment).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3643938&req=5

pone-0062562-g001: A multiple protein sequence alignment of the monolaris group from the I. scapularis sialome project [9].The multiple sequence alignment is based within the Cys framework showing the conserved Cys residues (black) and the arrow points to the oddly placed Cys position that depicts a potentially ‘atypical’ Cys motif in a monolaris protein described in the sialome of this tick – the asterisk denotes the missing Cys residue. All the monolaris sequences are named after their GenBank accession number and the ‘atypical’ sequence (DN971582) is shown last (at the bottom of the sequence alignment).
Mentions: Based on our sequence alignment of the conserved Cys residues in Kunitz domain peptides, we identified in the sialome project of Ribeiro et al. [14] a modified Kunitz among all the described I. scapularis monolaris sequences. Specifically, one sequence (GenBank: DN971582, the last sequence in Figure 1) is missing the initial conserved Cys residue that forms the first disulfide bridge of archetypical Kunitz peptides (denoted with an asterisk in Figure 1). Figure 1 also shows this peptide possessing an oddly positioned Cys (indicated by an arrow) that does not follow any Kunitz Cys motif found in I. scapularis sialome or previously described in the literature [45]. The Cys motif that this Kunitz displays is: CX(8)CX(4)CX(7)CX(12)CX(3)C.

Bottom Line: Using homology-based modeling (and other protein prediction programs) we were able to model and explain the multifaceted function of tryptogalinin.The N-terminus of the modeled tryptogalinin is detached from the rest of the peptide and exhibits intrinsic disorder allowing an increased flexibility for its high affinity with its inhibiting partners (i.e., serine proteases).By incorporating experimental and computational methods our data not only describes the function of a Kunitz peptide from Ixodes scapularis, but also allows us to hypothesize about the molecular basis of this function at the atomic level.

View Article: PubMed Central - PubMed

Affiliation: Institute of Parasitology, Biology Centre of the Academy of Sciences of the Czech Republic, České Budějovice, Czech Republic. valdjj@gmail.com

ABSTRACT

Background: A salivary proteome-transcriptome project on the hard tick Ixodes scapularis revealed that Kunitz peptides are the most abundant salivary proteins. Ticks use Kunitz peptides (among other salivary proteins) to combat host defense mechanisms and to obtain a blood meal. Most of these Kunitz peptides, however, remain functionally uncharacterized, thus limiting our knowledge about their biochemical interactions.

Results: We discovered an unusual cysteine motif in a Kunitz peptide. This peptide inhibits several serine proteases with high affinity and was named tryptogalinin due to its high affinity for β-tryptase. Compared with other functionally described peptides from the Acari subclass, we showed that tryptogalinin is phylogenetically related to a Kunitz peptide from Rhipicephalus appendiculatus, also reported to have a high affinity for β-tryptase. Using homology-based modeling (and other protein prediction programs) we were able to model and explain the multifaceted function of tryptogalinin. The N-terminus of the modeled tryptogalinin is detached from the rest of the peptide and exhibits intrinsic disorder allowing an increased flexibility for its high affinity with its inhibiting partners (i.e., serine proteases).

Conclusions: By incorporating experimental and computational methods our data not only describes the function of a Kunitz peptide from Ixodes scapularis, but also allows us to hypothesize about the molecular basis of this function at the atomic level.

Show MeSH