Amino Acid Side Chains Buried along Intersubunit Interfaces in a Viral Capsid Preserve Low Mechanical Stiffness Associated with Virus Infectivity
| Autor: | Pablo J. P. Carrillo, Rebeca Pérez, Mauricio G. Mateu, Alicia Rodríguez-Huete, Alejandro Valbuena, Milagros Castellanos, María Medrano |
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| Přispěvatelé: | Fundación Ramón Areces, Ministerio de Economía y Competitividad (España) |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Materials science Molecular structure and interactions viruses General Physics and Astronomy Mechanical properties Virus Stiffness Parvoviridae Infections 03 medical and health sciences Nanoparticle Capsid Side chain General Materials Science Amino Acids Alanine chemistry.chemical_classification biology Point mutation General Engineering Protein engineering biology.organism_classification Amino acid Crystallography 030104 developmental biology chemistry Minute Virus of Mice Biophysics Capsid Proteins Minute virus of mice |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 1936-086X 1936-0851 |
| DOI: | 10.1021/acsnano.6b08549 |
| Popis: | Single-molecule experimental techniques and theoretical approaches reveal that important aspects of virus biology can be understood in biomechanical terms at the nanoscale. A detailed knowledge of the relationship in virus capsids between small structural changes caused by single-point mutations and changes in mechanical properties may provide further physics-based insights into virus function; it may also facilitate the engineering of viral nanoparticles with improved mechanical behavior. Here, we used the minute virus of mice to undertake a systematic experimental study on the contribution to capsid stiffness of amino acid side chains at interprotein interfaces and the specific noncovalent interactions they establish. Selected side chains were individually truncated by introducing point mutations to alanine, and the effects on local and global capsid stiffness were determined using atomic force microscopy. The results revealed that, in the natural virus capsid, multiple, mostly hydrophobic, side chains buried along the interfaces between subunits preserve a comparatively low stiffness of most (S2 and S3) regions. Virtually no point mutation tested substantially reduced stiffness, whereas most mutations increased stiffness of the S2/S3 regions. This stiffening was invariably associated with reduced virus yields during cell infection. The experimental evidence suggests that a comparatively low stiffness at S3/S2 capsid regions may have been biologically selected because it facilitates capsid assembly, increasing infectious virus yields. This study demonstrated also that knowledge of individual amino acid side chains and biological pressures that determine the physical behavior of a protein nanoparticle may be used for engineering its mechanical properties. BIO2012-37649 and BIO2015-69928-R (MINECO/FEDER) to M.G.M., and an institutional grant from Fundación Ramón Areces to the Centro de Biología Molecular |
| Databáze: | OpenAIRE |
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