Insights into the functional expansion of the astacin peptidase family in parasitic helminths |
| |
| Affiliation: | 1. Intrahospital Infections Laboratory, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain;2. Parasitology Reference and Research Laboratory, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain;1. National Animal Protozoa Laboratory & College of Veterinary Medicine, China Agricultural University, Beijing 100193, China;2. Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China;3. Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA;4. Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;1. Public Health Agency of Canada, Agence de la Santé Publique du Canada, 200 René-Lévesque Blvd., Montréal, Québec H2Z 1X4, Canada;2. School of Public Health, University of Alberta, 357F South Academic Building, 116 St. and 85th Ave., Alberta T6G 2R3, Canada;3. Office of Campus Ministries, 110 E. 12th St. Hope College, Holland, MI 49423, United States;5. Saint Joseph High School, 2521 Stadium Dr., Saint Joseph, MI 49085, United States;1. General Zoology, Institute for Biology, Martin-Luther University Halle-Wittenberg, Hoher Weg 8, 06120 Halle (Saale), Germany;2. Laboratorio de Entomología Aplicada y Parasitología–LENAP, Escuela de Biología, Facultad de Farmacia, Universidad de San Carlos de Guatemala, Guatemala;3. Instituto de Investigaciones, Centro Universitario de Zacapa, Universidad de San Carlos de Guatemala, Guatemala;1. National Veterinary Research Institute in Pu?awy, Department of Parasitology and Invasive Diseases, Aleja Partyzantów 56, 24-100 Pu?awy, Poland;2. USDA-Agricultural Research Service, Animal Parasitic Diseases Lab, BARC-East Building 1040, 10300 Baltimore Avenue, 10705 Beltsville, MD, USA;1. Department of Botany and Zoology, Faculty of Science, Masaryk University, Brno, Czech Republic;2. Hasselt University, Centre for Environmental Sciences, Research Group Zoology: Biodiversity & Toxicology, Diepenbeek, Belgium;3. Institute of Biology, University of Graz, Universitätsplatz 2, A-8010 Graz, Austria;1. Mitrani Department of Desert Ecology, Swiss Institute for Dryland Environmental and Energy Research, Jacob Blaustein Institutes for Desert Research, Ben-Gurion University of the Negev, Sede Boqer Campus, Midreshet Ben-Gurion, Israel;2. French Associates Institute for Agriculture and Biotechnology of Drylands, Jacob Blaustein Institutes for Desert Research, Ben-Gurion University of the Negev, Sede Boqer Campus, Midreshet Ben-Gurion, Israel |
| |
| Abstract: | Helminths secrete a plethora of proteins involved in parasitism-related processes such as tissue penetration, migration, feeding and immunoregulation. Astacins, a family of zinc metalloproteases belonging to the peptidase family M12, are one of the most abundantly represented protein families in the secretomes of helminths. Despite their involvement in virulence, very few studies have addressed the role of this loosely defined protein group in parasitic helminths. Herein, we have analysed the predicted proteomes from 154 helminth species and confirmed the expansion of the astacin family in several nematode taxa. The astacin domain associated with up to 110 other domains into 145 unique domain architectures, where CUB and ShK constitute the principal and nearly independent bi-domain frameworks. The presence of co-existing domains suggests promiscuous adaptable functions to several roles. These activities could be related either to substrate specificity or to higher-order functions, such as anti-angiogenesis and immunomodulation, where the astacin domain would play an accessory role. Furthermore, some phylogenetically restricted mutations in the astacin domain affected residues located at the active cleft and binding sub-pockets, suggesting adaptation to different substrate specificities. Altogether, these findings suggest the astacin domain is a highly adaptable module that fulfils multiple proteolytic needs of the parasitic lifestyle. This study contributes to the understanding of helminth-secreted astacins and, ultimately, provides the foundation to guide future investigations about the role of this diverse family of proteins in host–parasite interactions. |
| |
| Keywords: | Astacin Domain fusion Helminth Phylogenetic analysis Parasite Protease |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
