Year: 2013
Type: article
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.
Source: PLoS ONE
Institutions: Institute of Parasitology, Czech Academy of Sciences, Biology Centre, Institució Catalana de Recerca i Estudis Avançats, Barcelona Supercomputing Center, Institute for Research in Biomedicine, National Institutes of Health, National Institute of Allergy and Infectious Diseases, University of California, Riverside
Language: English
Subfield: Parasitology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,382
Awards: G1736281816, G2112627551, G2397731120, Exploring the salivary transcriptome of Ixodes ricinus, the Lyme disease vector in Europe, and the potential role of its cystatins in pathogen transmission, G3303585017, Next-generation sequencing of salivary gland gene transcripts of Triatoma infestans for the discovery of triatomine exposure markers, G5883217300, G6311649877, G6461011143, Development of recombinant salivary antigens of Triatoma infestans for the detection of low-level infestation of triatomines, G6584597142, Rickettsial Immunity During Tick Transmission, Investigating the role of tick salivary protease inhibitors at the interface between ticks, pathogens and the vertebrate host
OpenAlex ID: W2006593248