Functional implications of the structure of the murine parvovirus, minute virus of mice.
BACKGROUND
Minute virus of mice (MVM) is a single-stranded (ss) DNA-containing, murine parvovirus with a capsid built up of 60 icosahedrally related polypeptide chains, each of which consists of the C-terminal region common to two structural proteins, VP1 and VP2. In infectious virions, most VP2 molecules are cleaved to VP3 by the removal of about 20 amino acids from the N terminus. Of the 587 amino acids in VP2, approximately half are identical to those in the analogous capsid protein of the antigenically distinct canine parvovirus (CPV), the crystal structure of which has previously been determined. The three-dimensional structure determination of MVMi (the immunosuppressive strain of MVM) was previously reported to 3.5 A resolution.


RESULTS
We report here an analysis of the MVMi virus structure and provide insights into tissue tropism, antigenicity and DNA packaging. Amino acids determining MVM tissue tropism were found to cluster on, or near, the viral surface. A conserved, glycine-rich, N-terminal peptide was seen to run through a cylindrical channel along each fivefold axis and may have implications for antigenicity. Density within the virion was interpreted as 29 ssDNA nucleotides per icosahedral asymmetric unit, and accounts for over one-third of the viral genome.


CONCLUSIONS
The presence of the glycine-rich sequence in the fivefold channels of MVMi provides a possible mechanism to explain how the unique N-terminal region of VP1 becomes externalized in infectious parvovirions. Residues that determine tropism may form an attachment recognition site for a secondary host-cell factor that modulates tissue specificity. The ordering of nucleotides in a similar region of the interior surface in the CPV and MVMi capsids suggests the existence of a genomic DNA-recognition site within the parvoviral capsid.
Agbandje-McKenna
M
M
Department of Biological Sciences, Purdue University, West Lafayette IN 47907-1392, USA.
Llamas-Saiz
A L
AL
Wang
F
F
Tattersall
P
P
Rossmann
M G
MG
D000595:Amino Acid Sequence; D002213:Capsid / Q000737:chemistry*; D036022:Capsid Proteins; D005998:Glycine / Q000737:chemistry; D008915:Minute Virus of Mice / Q000737:chemistry* / Q000502:physiology; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D018523:Tropism
D036022:Capsid Proteins; C095548:capsid protein VP2, parvovirus B19; D005998:Glycine