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Conformational variability of a picornavirus capsid: pH-dependent structural changes of Mengo virus related to its
S Kim1, U Boege, S Krishnaswamy
1Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907.
Abstract:
The structure of Mengo virus had been determined from crystals grown in the presence of 100 mM phosphate buffer at pH 7.4. It is shown that Mengo virus is poorly infectious at the phosphate concentration similar to that in which it was crystallized. Maximal infectivity is achieved at 10 mM phosphate or less in physiological saline. The phosphate effect is ameliorated when the pH is lowered to 4.6. Although it has not been possible to study the crystal structure of the virus at low phosphate concentrations, it is shown that increasing the Cl- concentration at pH 6.2 or decreasing the pH to 4.6 causes substantial conformational changes confined to the "pit," a deep surface depression. These structural changes involve a movement of the "FMDV loop" (GH loop) in VP1, an ordering of the "VP3 loop" (GH loop in VP3) between 3176 and 3182, the displacement of a bound phosphate near the "FMDV loop" (GH loop in VP1), and movement of the carboxy terminus of VP2. The changes in conformation are correlated with the dissociation of the virion into pentamers at pH 6.2 and 150 mM Cl-. The localization of the conformational changes and the correlated role of the phosphate in controlling infectivity support the hypothesis that the "pit" is the receptor attachment site.
Insights
Mengo virus infectivity is controlled by phosphate concentration and pH. Structural changes in the viral "pit" region at specific ion concentrations suggest it is the receptor attachment site.
Area of Science:
- Virology
- Structural Biology
- Biochemistry
Background:
- Mengo virus structure was previously determined using crystals with high phosphate concentrations.
- Viral infectivity is known to be influenced by environmental factors such as ion concentrations and pH.
Purpose of the Study:
- To investigate the relationship between Mengo virus structure, infectivity, and environmental conditions.
- To identify the specific viral region responsible for receptor attachment.
Main Methods:
- Crystallography to determine viral structure.
- Infectivity assays at varying phosphate and chloride concentrations and pH levels.
- Analysis of conformational changes using structural data.
Main Results:
- Mengo virus shows reduced infectivity at high phosphate concentrations (100 mM) and optimal infectivity at 10 mM or less.
- Lowering pH to 4.6 or increasing chloride concentration to 150 mM at pH 6.2 induces conformational changes in the viral
- pit
- These changes include movement of specific loops (VP1 GH loop, VP3 GH loop), phosphate displacement, and carboxy terminus VP2 movement.
- Conformational changes correlate with virion dissociation into pentamers under specific ionic conditions.
Conclusions:
- Phosphate concentration and pH significantly impact Mengo virus infectivity.
- The viral
- pit
- region undergoes conformational changes modulated by ion concentrations and pH.
- These findings support the hypothesis that the
- pit
- is the site of receptor attachment for Mengo virus.