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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Official URL: http://dx.doi.org/10.1016/j.jmb.2009.04.045

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that much of the loop structure of classical Kunitz domains, including the protruding protease-binding loop, has been replaced by β-strands.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
UKCEH and CEH Sections/Science Areas:	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 +0 (UTC)
URI:	https://nora.nerc.ac.uk/id/eprint/8582

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

UKCEH and CEH Sections/Science Areas:

Hails

ISSN:

0022-2836

Additional Keywords:

Rhipicephalus appendiculatus, salivary gland, Kunitz domains, maxiK channel activation, sulphur SAD