Molecular and structural characterization of novel cystatins from the taiga tick Ixodes persulcatus
| Autor: | Itabajara da Silva Vaz, Adriana Seixas, Carolina Konrdörfer Rangel, Gabriela Alves Sabadin, Masayoshi Isezaki, Luís Fernando Parizi, Naftaly Githaka, Evenilton Pessoa Costa, Nelilma C. Romeiro, Satoru Konnai, Kazuhiko Ohashi, Carlos Logullo |
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| Rok vydání: | 2017 |
| Předmět: |
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Molecular 0301 basic medicine Protein family Sequence analysis Cathepsin L Sequence alignment Ixodes persulcatus Tick Real-Time Polymerase Chain Reaction Microbiology Antibodies Arthropod Proteins 03 medical and health sciences Cricetinae Rhipicephalus Animals Humans Phylogeny Binding Sites Ixodes biology Sequence Analysis DNA biology.organism_classification Cystatins Virology Immunity Humoral Tick Infestations Molecular Docking Simulation 030104 developmental biology Infectious Diseases Multigene Family Insect Science Rhipicephalus microplus Parasitology Cystatin Sequence Alignment |
| Zdroj: | Ticks and Tick-borne Diseases. 8:432-441 |
| ISSN: | 1877-959X |
| DOI: | 10.1016/j.ttbdis.2017.01.007 |
| Popis: | Cystatins are cysteine peptidase inhibitors that in ticks mediate processes such as blood feeding and digestion. The ixodid tick Ixodes persulcatus is endemic to the Eurasia, where it is the principal vector of Lyme borreliosis. To date, no I. persulcatus cystatin has been characterized. In the present work, we describe three novel cystatins from I. persulcatus, named JpIpcys2a, JpIpcys2b and JpIpcys2c. In addition, the potential of tick cystatins as cross-protective antigens was evaluated by vaccination of hamsters using BrBmcys2c, a cystatin from Rhipicephalus microplus, against I. persulcatus infestation. Sequence analysis showed that motifs that are characteristic of cystatins type 2 are fully conserved in JpIpcys2b, while mutations are present in both JpIpcys2a and JpIpcys2c. Protein-protein docking simulations further revealed that JpIpcys2a, JpIpcys2b and JpIpcys2c showed conserved binding sites to human cathepsins L, all of them covering the active site cleft. Cystatin transcripts were detected in different I. persulcatus tissues and instars, showing their ubiquitous expression during I. persulcatus development. Serological analysis showed that although hamsters immunized with BrBmcys2c developed a humoral immune response, this response was not adequate to protect against a heterologous challenge with I. persulcatus adult ticks. The lack of cross-protection provided by BrBmcys2c immunization is perhaps linked to the fact that cystatins cluster into multigene protein families that are expressed differentially and exhibit functional redundancy. How to target such small proteins that are secreted in low quantities remains a challenge in the development of suitable anti-tick vaccine antigens. |
| Databáze: | OpenAIRE |
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