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The characteristics of rare codon clusters in the genome and proteins of hepatitis C virus; a bioinformatics look.

Fattahi M, Malekpour A, Mortazavi M, Safarpour A, Naseri N - Middle East J Dig Dis (2014)

Bottom Line: CONCLUSION The characteristics of these residues and their relative status showed that these rare codon clusters play an important role in proper folding of these proteins.Thus, it is likely that these rare codon clusters may have an important role in the function of HCV proteins.This information is helpful in development of new avenues for vaccine and treatment protocols.

View Article: PubMed Central - HTML - PubMed

Affiliation: Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

ABSTRACT
BACKGROUND Recent studies suggest that rare codon clusters are functionally important for protein activity. METHODS Here, for the first time we analyzed and reported rare codon clusters in Hepatitis C Virus (HCV) genome and then identified the location of these rare codon clusters in the structure of HCV protein. This analysis was performed using the Sherlocc program that detects statistically relevant conserved rare codon clusters. RESULTS By this program, we identified the rare codon cluster in three regions of HCV genome; NS2, NS3, and NS5A coding sequence of HCV genome. For further understanding of the role of these rare codon clusters, we studied the location of these rare codon clusters and critical residues in the structure of NS2, NS3 and NS5A proteins. We identified some critical residues near or within rare codon clusters. It should be mentioned that characteristics of these critical residues such as location and situation of side chains are important in assurance of the HCV life cycle. CONCLUSION The characteristics of these residues and their relative status showed that these rare codon clusters play an important role in proper folding of these proteins. Thus, it is likely that these rare codon clusters may have an important role in the function of HCV proteins. This information is helpful in development of new avenues for vaccine and treatment protocols.

No MeSH data available.


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Mentions: Also, for W35F and W35FNS3- Q221L, interaction of NS2 with other viral proteins reduced, but to different extents.43 Based on the model of the NS2, residues 25 and 39, which were found on TMS1 and TMS2, respectively, might be in contact.43 It assumed the ‘‘hole’’ created in TMS2 by the Y39A substitution was compensated by a bulky amino acid in the interacting TMS1 counterpart, thus ‘filling up’ the hole in the mutated TMS2. A striking correlation was found between reduction of aromaticity as well as size of residues at these sites (W35 and W36) and decrease of virus production arguing the aromatic side chains of W35 and W36 involved in essential interactions. These results show that these residues play critical roles in proper folding of this protein and disrupting this process severely affected the virus life cycle. An important point deduced from our analysis was that some of these residues were involved in rare codon clusters of NS2 (figure 6).


The characteristics of rare codon clusters in the genome and proteins of hepatitis C virus; a bioinformatics look.

Fattahi M, Malekpour A, Mortazavi M, Safarpour A, Naseri N - Middle East J Dig Dis (2014)

© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4208930&req=5

Mentions: Also, for W35F and W35FNS3- Q221L, interaction of NS2 with other viral proteins reduced, but to different extents.43 Based on the model of the NS2, residues 25 and 39, which were found on TMS1 and TMS2, respectively, might be in contact.43 It assumed the ‘‘hole’’ created in TMS2 by the Y39A substitution was compensated by a bulky amino acid in the interacting TMS1 counterpart, thus ‘filling up’ the hole in the mutated TMS2. A striking correlation was found between reduction of aromaticity as well as size of residues at these sites (W35 and W36) and decrease of virus production arguing the aromatic side chains of W35 and W36 involved in essential interactions. These results show that these residues play critical roles in proper folding of this protein and disrupting this process severely affected the virus life cycle. An important point deduced from our analysis was that some of these residues were involved in rare codon clusters of NS2 (figure 6).

Bottom Line: CONCLUSION The characteristics of these residues and their relative status showed that these rare codon clusters play an important role in proper folding of these proteins.Thus, it is likely that these rare codon clusters may have an important role in the function of HCV proteins.This information is helpful in development of new avenues for vaccine and treatment protocols.

View Article: PubMed Central - HTML - PubMed

Affiliation: Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

ABSTRACT
BACKGROUND Recent studies suggest that rare codon clusters are functionally important for protein activity. METHODS Here, for the first time we analyzed and reported rare codon clusters in Hepatitis C Virus (HCV) genome and then identified the location of these rare codon clusters in the structure of HCV protein. This analysis was performed using the Sherlocc program that detects statistically relevant conserved rare codon clusters. RESULTS By this program, we identified the rare codon cluster in three regions of HCV genome; NS2, NS3, and NS5A coding sequence of HCV genome. For further understanding of the role of these rare codon clusters, we studied the location of these rare codon clusters and critical residues in the structure of NS2, NS3 and NS5A proteins. We identified some critical residues near or within rare codon clusters. It should be mentioned that characteristics of these critical residues such as location and situation of side chains are important in assurance of the HCV life cycle. CONCLUSION The characteristics of these residues and their relative status showed that these rare codon clusters play an important role in proper folding of these proteins. Thus, it is likely that these rare codon clusters may have an important role in the function of HCV proteins. This information is helpful in development of new avenues for vaccine and treatment protocols.

No MeSH data available.


Related in: MedlinePlus