Modulation of the pH Stability of Influenza Virus Hemagglutinin: A Host Cell Adaptation Strategy
Proteins undergo dynamic structural changes to function within the range of physical and chemical conditions of their microenvironments. Changes in these environments affect their activity unless the respective mutations preserve their proper function. Here, we examine the influenza A virus spike pr...
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2016
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00063495_v110_n11_p2293_DiLella http://hdl.handle.net/20.500.12110/paper_00063495_v110_n11_p2293_DiLella |
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paper:paper_00063495_v110_n11_p2293_DiLella2023-06-08T14:31:15Z Modulation of the pH Stability of Influenza Virus Hemagglutinin: A Host Cell Adaptation Strategy Influenza virus hemagglutinin adaptation animal genetics human Influenza A virus metabolism pH physiology protein stability virus entry Adaptation, Biological Animals Hemagglutinin Glycoproteins, Influenza Virus Humans Hydrogen-Ion Concentration Influenza A virus Protein Stability Virus Internalization Proteins undergo dynamic structural changes to function within the range of physical and chemical conditions of their microenvironments. Changes in these environments affect their activity unless the respective mutations preserve their proper function. Here, we examine the influenza A virus spike protein hemagglutinin (HA), which undergoes a dynamic conformational change that is essential to the viral life cycle and is dependent on endosomal pH. Since the cells of different potential hosts exhibit different levels of pH, the virus can only cross species barriers if HA undergoes mutations that still permit the structural change to occur. This key event occurs after influenza A enters the host cell via the endocytic route, during its intracellular transport inside endosomes. The acidic pH inside these vesicles triggers a major structural transition of HA that induces fusion of the viral envelope and the endosomal membrane, and permits the release of the viral genome. HA experiences specific mutations that alter its pH stability and allow the conformational changes required for fusion in different hosts, despite the differences in the degree of acidification of their endosomes. Experimental and theoretical studies over the past few years have provided detailed insights into the structural aspects of the mutational changes that alter its susceptibility to different pH thresholds. We will illustrate how such mutations modify the protein's structure and consequently its pH stability. These changes make HA an excellent model of the way subtle structural modifications affect a protein's stability and enable it to function in diverse environments. © 2016 Biophysical Society. 2016 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00063495_v110_n11_p2293_DiLella http://hdl.handle.net/20.500.12110/paper_00063495_v110_n11_p2293_DiLella |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Influenza virus hemagglutinin adaptation animal genetics human Influenza A virus metabolism pH physiology protein stability virus entry Adaptation, Biological Animals Hemagglutinin Glycoproteins, Influenza Virus Humans Hydrogen-Ion Concentration Influenza A virus Protein Stability Virus Internalization |
| spellingShingle |
Influenza virus hemagglutinin adaptation animal genetics human Influenza A virus metabolism pH physiology protein stability virus entry Adaptation, Biological Animals Hemagglutinin Glycoproteins, Influenza Virus Humans Hydrogen-Ion Concentration Influenza A virus Protein Stability Virus Internalization Modulation of the pH Stability of Influenza Virus Hemagglutinin: A Host Cell Adaptation Strategy |
| topic_facet |
Influenza virus hemagglutinin adaptation animal genetics human Influenza A virus metabolism pH physiology protein stability virus entry Adaptation, Biological Animals Hemagglutinin Glycoproteins, Influenza Virus Humans Hydrogen-Ion Concentration Influenza A virus Protein Stability Virus Internalization |
| description |
Proteins undergo dynamic structural changes to function within the range of physical and chemical conditions of their microenvironments. Changes in these environments affect their activity unless the respective mutations preserve their proper function. Here, we examine the influenza A virus spike protein hemagglutinin (HA), which undergoes a dynamic conformational change that is essential to the viral life cycle and is dependent on endosomal pH. Since the cells of different potential hosts exhibit different levels of pH, the virus can only cross species barriers if HA undergoes mutations that still permit the structural change to occur. This key event occurs after influenza A enters the host cell via the endocytic route, during its intracellular transport inside endosomes. The acidic pH inside these vesicles triggers a major structural transition of HA that induces fusion of the viral envelope and the endosomal membrane, and permits the release of the viral genome. HA experiences specific mutations that alter its pH stability and allow the conformational changes required for fusion in different hosts, despite the differences in the degree of acidification of their endosomes. Experimental and theoretical studies over the past few years have provided detailed insights into the structural aspects of the mutational changes that alter its susceptibility to different pH thresholds. We will illustrate how such mutations modify the protein's structure and consequently its pH stability. These changes make HA an excellent model of the way subtle structural modifications affect a protein's stability and enable it to function in diverse environments. © 2016 Biophysical Society. |
| title |
Modulation of the pH Stability of Influenza Virus Hemagglutinin: A Host Cell Adaptation Strategy |
| title_short |
Modulation of the pH Stability of Influenza Virus Hemagglutinin: A Host Cell Adaptation Strategy |
| title_full |
Modulation of the pH Stability of Influenza Virus Hemagglutinin: A Host Cell Adaptation Strategy |
| title_fullStr |
Modulation of the pH Stability of Influenza Virus Hemagglutinin: A Host Cell Adaptation Strategy |
| title_full_unstemmed |
Modulation of the pH Stability of Influenza Virus Hemagglutinin: A Host Cell Adaptation Strategy |
| title_sort |
modulation of the ph stability of influenza virus hemagglutinin: a host cell adaptation strategy |
| publishDate |
2016 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00063495_v110_n11_p2293_DiLella http://hdl.handle.net/20.500.12110/paper_00063495_v110_n11_p2293_DiLella |
| _version_ |
1768542344952414208 |