Molecular Determinants of Self-Association and Rearrangement of a Trimeric Intermediate during the Assembly of a Parvovirus Capsid.
Summary of "Molecular Determinants of Self-Association and Rearrangement of a Trimeric Intermediate during the Assembly of a Parvovirus Capsid."
The minute virus of mice (MVM) provides a simple model for the dissection of the molecular determinants of the self-assembly, stability, and dynamics of a biological supramolecular complex. MVM assembly involves the trimerization of capsid subunits in the cytoplasm; trimers are transported to the nucleus, where they suffer a conformational change and are made competent for capsid formation. Our previous study revealed that capsid assembly from trimers is dependent on stronger intertrimer interactions that are equally spaced in an equatorial belt surrounding each trimer. We have now targeted the interfaces between monomers within each trimer to identify the molecular determinants of trimerization and the rearrangement needed for capsid assembly. Twenty-eight amino acid residues per monomer were individually mutated to alanine to remove most of the stronger intersubunit interactions. The effects on trimer and capsid assembly and virus infectivity in cells were analyzed. No side chain was individually required for trimer assembly in the cytoplasm; in contrast, half of them were required to make the trimers competent for nuclear capsid assembly, even though none was close to intertrimer interfaces. These critical side chains are conserved and participate in extensive hydrophobic contacts, buried hydrogen bonds, or salt bridges between subunits. This study on MVM capsid assembly reveals that: (i) trimerization is a robust process, insensitive to removal of individual intersubunit interactions; and (ii) the rearrangement of the trimer intermediate required for capsid assembly is a global process that depends on the establishment of many interactions along the protein-protein interfaces within each trimer.
Affiliation
Journal Details
This article was published in the following journal.
Name: Journal of molecular biology
ISSN: 1089-8638
Pages: 32-40
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21867712
- DOI: http://dx.doi.org/10.1016/j.jmb.2011.08.020
Medical and Biotech [MESH] Definitions
Gene Rearrangement, T-lymphocyte
Ordered rearrangement of T-cell variable gene regions coding for the antigen receptors.
Gene Rearrangement
The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development.
Antibody Specificity
The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.
Gene Rearrangement, B-lymphocyte
Ordered rearrangement of B-lymphocyte variable gene regions coding for the IMMUNOGLOBULIN CHAINS, thereby contributing to antibody diversity. It occurs during the differentiation of the IMMATURE B-LYMPHOCYTES.
Gene Rearrangement, B-lymphocyte, Heavy Chain
Ordered rearrangement of B-lymphocyte variable gene regions of the IMMUNOGLOBULIN HEAVY CHAINS, thereby contributing to antibody diversity. It occurs during the first stage of differentiation of the IMMATURE B-LYMPHOCYTES.
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