2jqg
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(New page: 200px<br /><applet load="2jqg" size="450" color="white" frame="true" align="right" spinBox="true" caption="2jqg" /> '''Leader Protease'''<br /> ==Overview== The l...)
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Revision as of 10:32, 21 November 2007
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Leader Protease
Overview
The leader protease (Lb(pro)) of foot-and-mouth disease virus frees itself, during translation from the viral polyprotein by cleavage between its own, C terminus and the N terminus of the subsequent protein, VP4. Lb(pro) also, specifically cleaves the host proteins eukaryotic initiation factor (eIF), 4GI and 4GII, thus disabling host cell protein synthesis. We used NMR to, study full-length Lb(pro) as well as a shortened species lacking six, C-terminal amino acid residues (sLb(pro)) to examine the mechanism of, self-processing, the quaternary structure and the substrate specificity., Both Lb(pro) forms have the same structure in solution as in the crystal., In the solution structure of sLb(pro), the 12 residue C-terminal extension, was flexible and disordered. In contrast, the 18 residue C-terminal, extension of full-length Lb(pro) was bound by the substrate-binding site, of a neighbouring molecule, resulting in the formation of a stable dimer, in solution. The Lb(pro) dimer could not be dissociated by increasing the, ionic strength or by dilution. Furthermore, titration with model peptides, mimicking the substrates destabilised the dimer interface without, dissociating the dimer. The peptides were, however, bound by sLb(pro) in, the canonical substrate binding site. Peptide binding gave rise to, chemical shifts of residues around the sLb(pro) substrate binding site., Shifts of Asn146 and Glu147 indicated that these residues might form the, enzyme's S1' site and interact with the P1' arginine residue of the eIF4GI, cleavage site. Furthermore, differences in substrate specificity between, sLb(pro) and Lb(pro) observed with an in vitro translated protein indicate, some involvement of the C terminus in substrate recognition.
About this Structure
2JQG is a Single protein structure of sequence from Foot-and-mouth disease virus. Full crystallographic information is available from OCA.
Reference
Investigating the Substrate Specificity and Oligomerisation of the Leader Protease of Foot and Mouth Disease Virus using NMR., Cencic R, Mayer C, Juliano MA, Juliano L, Konrat R, Kontaxis G, Skern T, J Mol Biol. 2007 Nov 2;373(4):1071-87. Epub 2007 Sep 1. PMID:17897674
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