Myristylation of picornavirus capsid protein VP4 and its structural significance

Chow, Marie; Newman, J. F. E.; Filman, David J.; Hogle, James M.; Rowlands, David J.; Brown, F.

doi:10.1038/327482a0

Cited by 458 publications

(303 citation statements)

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“…In the case of the transforming protein of Rous sarcoma virus (pp60""c), the myristyl group is clearly necessary, although perhaps not sufficient, to convey membrane-associating properties (Kaplan et al, 1990). In the case of the poliovirus capsid protein, VP4, the myristyl group appears to provide a hydrophobic anchor between subunits on the coat surface and plays a structural role in capsid assembly (Chow et al, 1987). The structure of the mammalian C-subunit provides the first example of how a myristyl group can contribute to the stability of a soluble protein.…”

Section: Myristylationmentioning

confidence: 99%

Crystal structures of the myristylated catalytic subunit of cAMP‐dependent protein kinase reveal open and closed conformations

et al. 1993

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Three crystal structures, representing two distinct conformational states, of the mammalian catalytic subunit of CAMP-dependent protein kinase were solved using molecular replacement methods starting from the refined structure of the recombinant catalytic subunit ternary complex (Zheng, J., et al., 1993a, Biochemistry 32,2154-2161). These structures correspond to the free apoenzyme, a binary complex with an iodinated inhibitor peptide, and a ternary complex with both ATP and the unmodified inhibitor peptide. The apoenzyme and the binary complex crystallized in an open conformation, whereas the ternary complex crystallized in a closed conformation similar to the ternary complex of the recombinant enzyme. The model of the binary complex, refined at 2.9 A resolution, shows the conformational changes associated with the open conformation. These can be described by a rotation of the small lobe and a displacement of the C-terminal30 residues. This rotation of the small lobe alters the cleft interface in the active-site region surrounding the glycine-rich loop and Thr 197, a critical phosphorylation site. In addition to the conformational changes, the myristylation site, absent in the recombinant enzyme, was clearly defined in the binary complex. The myristic acid binds in a deep hydrophobic pocket formed by four segments of the protein that are widely dispersed in the linear sequence. The N-terminal40 residues that lie outside the conserved catalytic core are anchored by the N-terminal myristylate plus an amphipathic helix that spans both lobes and is capped by Trp 30. Both posttranslational modifications, phosphorylation and myristylation, contribute directly to the stable structure of this enzyme.

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Section: Myristylationmentioning

confidence: 99%

Crystal structures of the myristylated catalytic subunit of cAMP‐dependent protein kinase reveal open and closed conformations

et al. 1993

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“…However, not all myristylated proteins are membrane bound and myristylation in some cases is not sufficient for association with the lipid bilayer [32]. In addition, structural studies of the N-myristylated picornavirus capsid protein VP4 have shown that the fatty acid resides in a hydrophobic pocket formed by amino acid side chains [33]. Since alkaline extraction readily removes the 43 kDa protein from the membrane without modification of the myristylated Nterminus [28], Carr et al [29] have suggested that the fatty acid does not anchor 43 kDa protein to the membrane by imbedding in the lipid bilayer, but may instead be important in interactions between the 43 kDa protein and the AChR.…”

Section: Northern Blot Analysismentioning

confidence: 99%

Expression of RNA transcripts for the postsynaptic 43 kDa protein in innervated and denervated rat skeletal muscle

Froehner

1989

FEBS Letters

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A cDNA clone encoding the mouse muscle postsynaptic 43 kDa protein was isolated and sequenced. The amino acid sequence of this protein, which is closely associated with nicotinic acetylcholine receptors at Torpedo electrocyte and vertebrate skeletal muscle synapses, is very similar in different species. A cysteine-rich region homologous to part of the regulatory domain of protein kinase C may be important in interactions of this protein with the lipid bilayer. RNA transcripts for the 43 kDa protein increase only 2-3-fold after denervation of rat skeletal muscle, in sharp contrast to the a-subunit of the muscle nicotinic receptor which increases more than 30-fold. Thus, the expression of these two proteins is regulated by different mechanisms.

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“…One or two copies of VP0 remain uncleaved in each capsid, the functional significance of this observation being unclear. Picornavirus proteins are non-glycosylated but VP4 (and VP0) is modified at its N terminus by linkage to myristic acid (Chow et al, 1987). This fatty acid has been shown to be associated with viruses of several different families, and an involvement in receptor binding, uncoating or capsid assembly has been suggested (Chow et al, 1987).…”

Section: Structure Of Picornavirusesmentioning

confidence: 99%

“…Picornavirus proteins are non-glycosylated but VP4 (and VP0) is modified at its N terminus by linkage to myristic acid (Chow et al, 1987). This fatty acid has been shown to be associated with viruses of several different families, and an involvement in receptor binding, uncoating or capsid assembly has been suggested (Chow et al, 1987). In addition to this modification, the potential for VP2 and VP4 to be phosphorylated by cellular kinases, thereby destabilizing the capsid, may play a role in uncoating of the nucleic acid (Ratka et al, 1989).…”

Section: Structure Of Picornavirusesmentioning

confidence: 99%

Structure, function and evolution of picornaviruses

Stanway

1990

Journal of General Virology

161

105

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Myristylation of picornavirus capsid protein VP4 and its structural significance

Cited by 458 publications

References 0 publications

Crystal structures of the myristylated catalytic subunit of cAMP‐dependent protein kinase reveal open and closed conformations

Crystal structures of the myristylated catalytic subunit of cAMP‐dependent protein kinase reveal open and closed conformations

Expression of RNA transcripts for the postsynaptic 43 kDa protein in innervated and denervated rat skeletal muscle

Structure, function and evolution of picornaviruses

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