Structural studies on the mechanisms of antibody-mediated neutralization of human rhinovirus |
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| Institution: | 1. Department of Biological Sciences, Purdue University, West Lafayette, IN, 47907-1392;2. *Institute for Molecular Virology, University of Wisconsin, Madison, WI, 53706, USA;1. European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany;2. European Molecular Biology Laboratory (EMBL), GeneCore, Heidelberg, Germany;3. Division of Computational Genomics and Systems Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany;4. Faculty for Biosciences, Heidelberg University, Heidelberg, Germany;5. HIDSS4Health, Helmholtz Information and Data Science School for Health, Heidelberg, Germany;6. European Molecular Biology Laboratory (EMBL), European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK;7. Group “Genome Instability in Tumors,” German Cancer Research Center (DKFZ), Heidelberg, Germany;8. Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin, Berlin, Germany;9. National Center for Tumor Diseases (NCT), Heidelberg, Germany;10. German Cancer Research Center (DKFZ), Heidelberg, Germany;11. German Cancer Consortium (DKTK), Heidelberg, Germany;12. Wellcome Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK;13. Bridging Research Division on Mechanisms of Genomic Variation and Data Science, DKFZ, Heidelberg, Germany;14. Experimental and Clinical Research Center (ECRC) of the Max Delbrück Center (MDC) and Charité-Universitätsmedizin, Berlin, Germany;15. Freie Universität Berlin, Berlin, Germany;16. German Cancer Consortium (DKTK), partner site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany;1. LOF, Université Bordeaux 1, UMR CNRS-Rhodia-UB1 5258, 178, Avenue du docteur Schweitzer, 33608 Pessac Cedex, France;2. I2M, Département TREFLE, UMR CNRS 5295 – Site ENSAM Esplanade des Arts et Métiers, 33405 Talence Cedex, France;1. Key Laboratory of Radiation Physics and Technology of the Ministry of Education, Institute of Nuclear Science and Technology, College of Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610064, China;2. Biotechnology and Nuclear Technology Research Institute, Sichuan Academy of Agricultural Sciences, Chengdu 610061, China;1. Priority Research Centre for Healthy Lungs, Faculty of Health and Medicine, University of Newcastle, Newcastle, Australia;2. Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States;1. Department of Midwifery, Poltekkes Kemenkes Makassar, Indonesia;2. Proffession Midwife Study Program, Megarezky University, Indonesia;3. Doctoral Program,Faculty of Medicine, Hasanuddin University, Makassar 90245, Indonesia;4. Proffession Nurse Study Program, Megarezky University, Indonesia;1. Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan;2. Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan;3. Genomics Research Center, Academia Sinica, Taipei, Taiwan |
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| Abstract: | Antibodies represent a major component of the mammalian immunological defense against picornavirus infection. The work reviewed here examines structural details of antibody-mediated neutralization of human rhinovirus 14 (HRV14) using a combination of crystallography, molecular biology and electron microscopy. The atomic structures of the Fab fragment from a neutralizing monoclonal antibody (Fab17-IA) and HRV14 were used to interpret the ∼25Å resolution cryo-electron microscopy structure of the Fab17-IA/HRV14 complex. While there were not any observable antibody-induced conformational changes in the HRV14 upon antibody binding, there was evidence that charge interactions dominate the paratope-epitope interface and that the intact antibody might bind bivalently across icosahedral two-fold axes. Site-directed mutagenesis results confirmed that charge interactions dominate antibody binding and electron microscopy studies on the mAb17-IA/HRV14 complex confirmed that this neutralizing antibody binds bivalently across icosahedral two-fold axes. |
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