2W8X

Structure of the tick ion-channel modulator Ra-KLP

Summary for 2W8X

• Entry DOI: 10.2210/pdb2w8x/pdb
• Descriptor: ION-CHANNEL MODULATOR RAKLP, GLYCEROL, ACETATE ION, ... (5 entities in total)
• Functional Keywords: salivary gland, kunitz domains, maxik channel activation, sulphur sad, membrane protein
• Biological source: RHIPICEPHALUS APPENDICULATUS (TICK)
• Total number of polymer chains: 2
• Total formula weight: 17058.89

Authors

Paesen, G.C.,Siebold, C.,Dallas, M.,Peers, C.,Harlos, K.,Nuttall, P.A.,Nunn, M.A.,Stuart, D.I.,Esnouf, R.M. (deposition date: 2009-01-20, release date: 2009-05-05, Last modification date: 2024-11-06)

Primary citation

Paesen, G.C.,Siebold, C.,Dallas, M.L.,Peers, C.,Harlos, K.,Nuttall, P.A.,Nunn, M.A.,Stuart, D.I.,Esnouf, R.M.
An Ion-Channel Modulator from the Saliva of the Brown Ear Tick Has a Highly Modified Kunitz/Bpti Structure.
J.Mol.Biol., 389:734-, 2009

PubMed 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 A 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that much of the loop structure of classical Kunitz domains, including the protruding protease-binding loop, has been replaced by beta-strands.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 beta-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.

PubMed: 19394347
DOI: 10.1016/J.JMB.2009.04.045

Experimental method

X-RAY DIFFRACTION (1.6 Å)