The attachment of myristic acid to the N-terminal glycine residue of many
eukaryotic and viral proteins is often essential for the acquisition of the protein's
biological activity. Vaccinia virus (VV), the prototype member of the Poxviridae,
expresses several myristylated proteins during the course of infection. Only one of
these proteins, L1R, has been identified and characterized.
Experiments were performed to identify and analyze four additional VV
myristylproteins. These proteins were identified as the A-type inclusion protein (92
kDa), G9R (39 kDa), A16L (36 kDa), and E7R (17 kDa). The latter three proteins
were shown to be myristylated on an N-terminal glycine residue. Additional studies
demonstrated that both A16L and E7R are soluble proteins, unlike L1R, which is a
constituent of the viral envelope. Furthermore, A16L could not be detected in either purified extracellular enveloped virus (EEV) or in intracellular mature virus (IMV).
These are the two predominant forms of infectious virions produced during a VV
infection. E7R was detected in EEV and, to a lesser extent, in IMV.
Unlike the other proteins, the amino terminal sequence of the A-type inclusion
protein did not fit the consensus sequence for N-myristylation (M-G-X-X-X-S/T/A/C/N), suggesting that it was internally myristylated. A combination of studies
revealed that the protein is both myristylated and palmitylated. Addition of each acyl
group could be separated temporally: myristylation occured co-translationally, while
palmitylation occurred post-translationally. Genetic analyses of lysine doublets and
arginine/lysine doublets within the A-type inclusion protein indicated that these sites
are not utilized for myristylation. This is in contrast to the precursors of TNFoc and Ilia
which are internally-myristylated on a lysine doublet.
It is not clear why this protein would be both myristylated and palmitylated.
Only class four palmitylproteins, such as the Src family of proteins, have been shown
to be both myristylated and palmitylated. The A-type inclusion protein expressed by
cowpox virus forms a large symmetrical matix in the cytoplasm of infected cells and
generally contains mature virions. It is possible, therefore, that the function of
acylation may be to stabilize the protein matrix or to assist in occlusion of enveloped
virus particles. / Graduation date: 1998
| Identifer | oai:union.ndltd.org:ORGSU/oai:ir.library.oregonstate.edu:1957/33994 |
| Date | 21 April 1997 |
| Creators | Martin, Karen H. |
| Contributors | Hruby, Dennis E. |
| Source Sets | Oregon State University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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