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An Ion-channel Modulator from the Saliva of the Brown Ear Tick has a Highly Modified Kunitz/BPTI Structure

DOI: 10.1016/j.jmb.2009.04.045 DOI Help

Authors: Guido C. Paesen (CEH Oxford) , Christian Siebold (University of Oxford) , Mark L. Dallas (University of Leeds) , Chris Peers (University of Leeds) , Karl Harlos (University of Oxford) , Patricia A. Nuttall (CEH Oxford) , Miles A. Nunn (CEH Oxford) , David I. Stuart (University of Oxford) , Robert Esnouf (University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Molecular Biology , VOL 389 , PAGES 734-747

State: Published (Approved)
Published: June 2009

Abstract: 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that much of the loop structure of classical Kunitz domains, including the protruding protease-binding loop, has been replaced by ?-strands.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 ?-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.

Journal Keywords: Rhipicephalus Appendiculatus; Salivary Gland; Kunitz Domains; Maxik Channel Activation; Sulphur Sad

Subject Areas: Biology and Bio-materials

Facility: SRS

Added On: 23/06/2010 13:51

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