title: Structural tolerance versus functional intolerance to mutation of hydrophobic core residues surrounding cavities in a parvovirus capsid.
abstract: The structural and functional relevance of amino acid residues surrounding cavities within the hydrophobic core of the protein subunits that form the capsid of parvoviruses has been investigated. Several of the evolutionarily conserved, hydrophobic residues that delimit these cavities in the capsid of the minute virus of mice were replaced by other hydrophobic residues that would affect the size and/or shape of the cavity. When four or more methylene-sized groups were introduced, or six or more groups removed, capsid assembly was drastically impaired. In contrast, the introduction or removal of up to three groups had no significant effect on capsid assembly or thermostability. However, many of these mutations affected a capsid conformational transition needed for viral infectivity. Replacement of some polar residues around the largest cavity showed that capsid assembly requires a carboxylate buried within this cavity, but both aspartate and glutamate are structurally accepted. Again, only the aspartate allowed the production of infectious viruses, because of a specific role in encapsidation of the viral genome. These observations provide evidence of a remarkable structural tolerance to mutation of the hydrophobic core of the protein subunits in a viral capsid, and of an involvement of core residues and internal cavities in capsid functions needed for infectivity.
authors.affiliation: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autónoma de Madrid, Cantoblanco 28049 Madrid, Spain.
authors.forename: Aura
authors.initials: A
authors.lastname: Carreira
authors.forename: Mauricio G
authors.initials: MG
authors.lastname: Mateu
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D002213:Capsid / Q000378:metabolism / Q000648:ultrastructure; D036022:Capsid Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004279:DNA, Viral / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008915:Minute Virus of Mice / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009154:Mutation
chemical_list: D036022:Capsid Proteins; D004279:DNA, Viral