1nso
From Proteopedia
(New page: 200px<br /><applet load="1nso" size="450" color="white" frame="true" align="right" spinBox="true" caption="1nso" /> '''Folded monomer of protease from Mason-Pfizer...) |
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| - | [[Image:1nso.gif|left|200px]]<br /><applet load="1nso" size=" | + | [[Image:1nso.gif|left|200px]]<br /><applet load="1nso" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1nso" /> | caption="1nso" /> | ||
'''Folded monomer of protease from Mason-Pfizer monkey virus'''<br /> | '''Folded monomer of protease from Mason-Pfizer monkey virus'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The assembly of Mason-Pfizer monkey virus Gag polyproteins into immature | + | The assembly of Mason-Pfizer monkey virus Gag polyproteins into immature capsids and their cleavage by the encoded protease are temporally and spatially separated processes, making the virus a particularly useful model for investigation of protease activation. Here we present a high resolution NMR structure of a fully folded monomer of a 12 kDa M-PMV protease (wt 12 PR) and of a Cys7Ala/Asp26Asn/Cys106Ala mutant (12 PR(D26N/C7A/C106A)). The overall structures of both wt 12 PR and 12 PR(D26N/C7A/C106A) follow the conservative structural motif of other retroviral proteases. The most prominent difference from the canonical fold of retroviral proteases is the absence of the interfacial beta-sheet, which leads to the loss of the principal force stabilizing the dimer of M-PMV PR. The monomer-dimer equilibrium can be shifted in favor of the dimer by adding a substrate or an inhibitor, partially compensating for the missing role of the beta-sheet. We also show that cysteines C7 and C106 play a crucial role in stabilizing the dimer and consequently increasing the proteolytic activity of M-PMV PR. This is consistent with the role of reversible oxidative modification of the cysteine residues in the regulation of the maturation of assembled M-PMV capsids in the cytoplasm. |
==About this Structure== | ==About this Structure== | ||
| - | 1NSO is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Simian_retrovirus_2 Simian retrovirus 2]. Full crystallographic information is available from [http:// | + | 1NSO is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Simian_retrovirus_2 Simian retrovirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NSO OCA]. |
==Reference== | ==Reference== | ||
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[[Category: virus maturation]] | [[Category: virus maturation]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:09:36 2008'' |
Revision as of 12:09, 21 February 2008
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Folded monomer of protease from Mason-Pfizer monkey virus
Overview
The assembly of Mason-Pfizer monkey virus Gag polyproteins into immature capsids and their cleavage by the encoded protease are temporally and spatially separated processes, making the virus a particularly useful model for investigation of protease activation. Here we present a high resolution NMR structure of a fully folded monomer of a 12 kDa M-PMV protease (wt 12 PR) and of a Cys7Ala/Asp26Asn/Cys106Ala mutant (12 PR(D26N/C7A/C106A)). The overall structures of both wt 12 PR and 12 PR(D26N/C7A/C106A) follow the conservative structural motif of other retroviral proteases. The most prominent difference from the canonical fold of retroviral proteases is the absence of the interfacial beta-sheet, which leads to the loss of the principal force stabilizing the dimer of M-PMV PR. The monomer-dimer equilibrium can be shifted in favor of the dimer by adding a substrate or an inhibitor, partially compensating for the missing role of the beta-sheet. We also show that cysteines C7 and C106 play a crucial role in stabilizing the dimer and consequently increasing the proteolytic activity of M-PMV PR. This is consistent with the role of reversible oxidative modification of the cysteine residues in the regulation of the maturation of assembled M-PMV capsids in the cytoplasm.
About this Structure
1NSO is a Single protein structure of sequence from Simian retrovirus 2. Full crystallographic information is available from OCA.
Reference
Three-dimensional structure of a monomeric form of a retroviral protease., Veverka V, Bauerova H, Zabransky A, Lang J, Ruml T, Pichova I, Hrabal R, J Mol Biol. 2003 Oct 31;333(4):771-80. PMID:14568536
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