title: Tryptogalinin is a tick Kunitz serine protease inhibitor with a unique intrinsic disorder.
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.
authors: Institute of Parasitology, Biology Centre of the Academy of Sciences of the Czech Republic, České Budějovice, Czech Republic. valdjj@gmail.com
authors: James J
authors: JJ
authors: Valdés
authors: Alexandra
authors: A
authors: Schwarz
authors: Israel
authors: I
authors: Cabeza de Vaca
authors: Eric
authors: E
authors: Calvo
authors: Joao H F
authors: JH
authors: Pedra
authors: Victor
authors: V
authors: Guallar
authors: Michalis
authors: M
authors: Kotsyfakis
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D060829:Arthropod Proteins / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism; D003545:Cysteine / Q000737:chemistry / Q000235:genetics; D006801:Humans; D018884:Ixodes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism; D048494:Rhipicephalus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012471:Salivary Proteins and Peptides / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism; D053802:Tryptases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism
chemical_list: D060829:Arthropod Proteins; D011994:Recombinant Proteins; D012471:Salivary Proteins and Peptides; D015842:Serine Proteinase Inhibitors; D053802:Tryptases; D003545:Cysteine
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