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Protease-bound structure of Ricistatin provides insights into the mechanism of action of tick salivary cystatins in the vertebrate host

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F23%3A00580493" target="_blank" >RIV/60077344:_____/23:00580493 - isvavai.cz</a>

  • Alternative codes found

    RIV/61388963:_____/23:00580493 RIV/60076658:12310/23:43906690

  • Result on the web

    <a href="https://link.springer.com/article/10.1007/s00018-023-04993-4" target="_blank" >https://link.springer.com/article/10.1007/s00018-023-04993-4</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1007/s00018-023-04993-4" target="_blank" >10.1007/s00018-023-04993-4</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Protease-bound structure of Ricistatin provides insights into the mechanism of action of tick salivary cystatins in the vertebrate host

  • Original language description

    Tick saliva injected into the vertebrate host contains bioactive anti-proteolytic proteins from the cystatin family, however, the molecular basis of their unusual biochemical and physiological properties, distinct from those of host homologs, is unknown. Here, we present Ricistatin, a novel secreted cystatin identified in the salivary gland transcriptome of Ixodes ricinus ticks. Recombinant Ricistatin inhibited host-derived cysteine cathepsins and preferentially targeted endopeptidases, while having only limited impact on proteolysis driven by exopeptidases. Determination of the crystal structure of Ricistatin in complex with a cysteine cathepsin together with characterization of structural determinants in the Ricistatin binding site explained its restricted specificity. Furthermore, Ricistatin was potently immunosuppressive and anti-inflammatory, reducing levels of pro-inflammatory cytokines IL-6, IL-1 beta, and TNF-alpha and nitric oxide in macrophages, IL-2 and IL-9 levels in Th9 cells, and OVA antigen-induced CD4(+) T cell proliferation and neutrophil migration. This work highlights the immunotherapeutic potential of Ricistatin and, for the first time, provides structural insights into the unique narrow selectivity of tick salivary cystatins determining their bioactivity.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10608 - Biochemistry and molecular biology

Result continuities

  • Project

    Result was created during the realization of more than one project. More information in the Projects tab.

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2023

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Cellular and Molecular Life Sciences

  • ISSN

    1420-682X

  • e-ISSN

    1420-9071

  • Volume of the periodical

    80

  • Issue of the periodical within the volume

    11

  • Country of publishing house

    CH - SWITZERLAND

  • Number of pages

    17

  • Pages from-to

    339

  • UT code for WoS article

    001093315500001

  • EID of the result in the Scopus database

    2-s2.0-85174918368