Role of human Hv1 channels in sperm capacitation and white blood cell respiratory burst established by a designed peptide inhibitor
Year: 2018
Type: article
Abstract: Significance Some peptide toxins act by stabilizing the voltage sensor domains (VSDs) of voltage-gated channels in open or closed conformations. hHv1 is a human voltage-gated proton channel and has lacked a specific inhibitor to assess its roles in physiology. We designed a phage-display library of 1 million novel peptides sharing an inhibitor cysteine knot (ICK) scaffold by combining elements of natural toxins; phagemids expressing Corza6 (C6) were selected by their capacity to bind to hHv1 protein. Two C6 peptides bind to the two VSDs in hHv1 and thereby inhibit channel operation. C6 was employed to confirm hypothesized roles for hHv1 in human sperm and white blood cells. The method should prove amenable to designer toxin identification for other voltage-gated channels.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Funders: United States - Israel Binational Science Foundation, Consejo Nacional de Investigaciones Científicas y Técnicas, Ministerio de Ciencia, Tecnología e Innovación Productiva, Universidad Nacional de Cuyo, National Institutes of Health, Agencia Nacional de Promoción Científica y Tecnológica, National Institute of General Medical Sciences, Fondo para la Investigación Científica y Tecnológica
OpenAlex ID: W2902178703