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An ion-channel modulator from the saliva of the brown ear tick has a highly modified Kunitz/BPTI structure

Paesen, Guido C.; Siebold, Christian; Dallas, Mark L.; Peers, Chris; Harlos, Karl; Nuttall, Patricia A.; Nunn, Miles A.; Stuart, David I.; Esnouf, Robert M.. 2009 An ion-channel modulator from the saliva of the brown ear tick has a highly modified Kunitz/BPTI structure. Journal of Molecular Biology, 389 (4). 734-747. 10.1016/j.jmb.2009.04.045

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Abstract/Summary

Ra-KLP, a 75 amino acid protein secreted by the salivary gland of the brown ear tick Rhipicephalus appendiculatus has a sequence resembling those of Kunitz/BPTI proteins. We report the detection, purification and characterization of the function of Ra-KLP. In addition, determination of the three-dimensional crystal structure of Ra-KLP at 1.6 Å resolution using sulphur single-wavelength anomalous dispersion reveals that much of the loop structure of classical Kunitz domains, including the protruding protease-binding loop, has been replaced by β-strands. Even more unusually, the N-terminal portion of the polypeptide chain is pinned to the ”Kunitz head” by two disulphide bridges not found in classical Kunitz/BPTI proteins. The disulphide bond pattern has been further altered by the loss of the bridge that normally stabilizes the protease-binding loop. Consistent with the conversion of this loop into a β-strand, Ra-KLP shows no significant anti-protease activity; however, it activates maxiK channels in an in vitro system, suggesting a potential mechanism for regulating host blood supply during feeding.

Item Type: Publication - Article
Digital Object Identifier (DOI): 10.1016/j.jmb.2009.04.045
Programmes: CEH Programmes pre-2009 publications > Biodiversity > BD03 The Genetic Basis of Ecological Function > BD03.3 Molecular evolution and bioinformatics
CEH Sections: Hails
ISSN: 0022-2836
Additional Keywords: Rhipicephalus appendiculatus, salivary gland, Kunitz domains, maxiK channel activation, sulphur SAD
NORA Subject Terms: Biology and Microbiology
Date made live: 17 Feb 2010 15:54
URI: http://nora.nerc.ac.uk/id/eprint/8582

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