{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:24:47Z","timestamp":1787239487338,"version":"build-2736575974"},"reference-count":63,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T00:00:00Z","timestamp":1725580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Servicio para el Control de la Esterilizaci\u00f3n\/Laboratorio de Microbiolog\u00eda Oral (SCE\/LMO) of the University of Oviedo","award":["FUO-19-258"],"award-info":[{"award-number":["FUO-19-258"]}]},{"name":"Servicio para el Control de la Esterilizaci\u00f3n\/Laboratorio de Microbiolog\u00eda Oral (SCE\/LMO) of the University of Oviedo","award":["FUO-21-304"],"award-info":[{"award-number":["FUO-21-304"]}]},{"name":"Servicio para el Control de la Esterilizaci\u00f3n\/Laboratorio de Microbiolog\u00eda Oral (SCE\/LMO) of the University of Oviedo","award":["SV-03-FSCARRASCO"],"award-info":[{"award-number":["SV-03-FSCARRASCO"]}]},{"name":"Fundaci\u00f3n Sira Carrasco para la Ayuda a la Fibrosis Qu\u00edstica","award":["FUO-19-258"],"award-info":[{"award-number":["FUO-19-258"]}]},{"name":"Fundaci\u00f3n Sira Carrasco para la Ayuda a la Fibrosis Qu\u00edstica","award":["FUO-21-304"],"award-info":[{"award-number":["FUO-21-304"]}]},{"name":"Fundaci\u00f3n Sira Carrasco para la Ayuda a la Fibrosis Qu\u00edstica","award":["SV-03-FSCARRASCO"],"award-info":[{"award-number":["SV-03-FSCARRASCO"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human lactoferrin (hLf) is an innate host defense protein that inhibits microbial H+-ATPases. This protein includes an ancestral structural motif (i.e., \u03b3-core motif) intimately associated with the antimicrobial activity of many natural Cys-rich peptides. Peptides containing a complete \u03b3-core motif from hLf or other phylogenetically diverse antimicrobial peptides (i.e., afnA, SolyC, PA1b, PvD1, thanatin) showed microbicidal activity with similar features to those previously reported for hLf and defensins. Common mechanistic characteristics included (1) cell death independent of plasma membrane (PM) lysis, (2) loss of intracellular K+ (mediated by Tok1p K+ channels in yeast), (3) inhibition of microbicidal activity by high extracellular K+, (4) influence of cellular respiration on microbicidal activity, (5) involvement of mitochondrial ATP synthase in yeast cell death processes, and (6) increment of intracellular ATP. Similar features were also observed with the BM2 peptide, a fungal PM H+-ATPase inhibitor. Collectively, these findings suggest host defense peptides containing a homologous \u03b3-core motif inhibit PM H+-ATPases. Based on this discovery, we propose that the \u03b3-core motif is an archetypal effector involved in the inhibition of PM H+-ATPases across kingdoms of life and contributes to the in vitro microbicidal activity of Cys-rich antimicrobial peptides.<\/jats:p>","DOI":"10.3390\/ijms25179672","type":"journal-article","created":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T10:29:45Z","timestamp":1725618585000},"page":"9672","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Archetypal Gamma-Core Motif of Antimicrobial Cys-Rich Peptides Inhibits H+-ATPases in Target Pathogens"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7827-981X","authenticated-orcid":false,"given":"Mar\u00eda T.","family":"Andr\u00e9s","sequence":"first","affiliation":[{"name":"Laboratory of Oral Microbiology (LMO), Clinical University of Odontology (CLUO), University of Oviedo, 33006 Oviedo, Asturias, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), 33006 Oviedo, Asturias, Spain"},{"name":"SamerLabs SL, Asturias Technology Park, 33428 Llanera, Asturias, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nannette Y.","family":"Yount","sequence":"additional","affiliation":[{"name":"Divisions of Molecular Medicine and Infectious Diseases, Department of Medicine, Los Angeles County (LAC)\u2014Harbor University of California\u2014Los Angeles (UCLA) Medical Center, Torrance, CA 90502, USA"},{"name":"Institute for Infection & Immunity, Lundquist Institute for Biomedical Innovation at Harbor UCLA, Torrance, CA 90502, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9562-6887","authenticated-orcid":false,"given":"Maikel","family":"Acosta-Zald\u00edvar","sequence":"additional","affiliation":[{"name":"Laboratory of Oral Microbiology (LMO), Clinical University of Odontology (CLUO), University of Oviedo, 33006 Oviedo, Asturias, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Yeaman","sequence":"additional","affiliation":[{"name":"Divisions of Molecular Medicine and Infectious Diseases, Department of Medicine, Los Angeles County (LAC)\u2014Harbor University of California\u2014Los Angeles (UCLA) Medical Center, Torrance, CA 90502, USA"},{"name":"Institute for Infection & Immunity, Lundquist Institute for Biomedical Innovation at Harbor UCLA, Torrance, CA 90502, USA"},{"name":"Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2752-0690","authenticated-orcid":false,"given":"Jos\u00e9 F.","family":"Fierro","sequence":"additional","affiliation":[{"name":"Laboratory of Oral Microbiology (LMO), Clinical University of Odontology (CLUO), University of Oviedo, 33006 Oviedo, Asturias, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), 33006 Oviedo, Asturias, Spain"},{"name":"Department of Functional Biology (Microbiology), Faculty of Medicine, University of Oviedo, 33006 Oviedo, Asturias, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.bbagen.2011.06.002","article-title":"Molecular evolution of the transferrin family and associated receptors","volume":"1820","author":"Lambert","year":"2012","journal-title":"Biochim. 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