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Article: The Y271 and I274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability
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TitleThe Y271 and I274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability
 
AuthorsZhang, HJ1
Wang, YX2
Wu, H1
Jin, DY1
Wen, YM2
Zheng, BJ1
 
Issue Date2009
 
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
 
CitationPlos One, 2009, v. 4 n. 7 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pone.0006108
 
AbstractReverse transcriptase (RT) of human immunodeficiency virus (HIV)-1 plays a key role in initiating viral replication and is an important target for developing anti-HIV drugs. Our previous study showed that two mutations (Y271A and I274A) in the turn RT (Gln 269-Arg 277) abrogated viral replication, but the replication capacity and RT activity was discordant. In this study, we further investigated why alanine substitutions at these two sites would affect viral replication. We found that both RT activity and RT protein were almost undetectable in viral particles of these two mutants, although the Pr160 gag-pol mutants were properly expressed, transported and incorporated. Using protease inhibition assay, we demonstrated a correlation between the degradation of the RT mutants and the activity of viral protease. Our native gel analysis indicated that the mutations at 271 and 274 amino acids might cause conformational changes, leading to the formation of higher order oligomers instead of dimers, resulting in increased protein instability and susceptibility to viral protease. Thus, residues 271 and 274 are critical to RT stability and resistance to viral protease. The conservation of the two amino acid residues among different strains of HIV-1 lent further support to this conclusion. The knowledge gained here may prove useful in drug design. © 2009 Zhang et al.
 
ISSN1932-6203
2012 Impact Factor: 3.73
2012 SCImago Journal Rankings: 1.512
 
DOIhttp://dx.doi.org/10.1371/journal.pone.0006108
 
PubMed Central IDPMC2701634
 
ISI Accession Number IDWOS:000267806300001
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorZhang, HJ
 
dc.contributor.authorWang, YX
 
dc.contributor.authorWu, H
 
dc.contributor.authorJin, DY
 
dc.contributor.authorWen, YM
 
dc.contributor.authorZheng, BJ
 
dc.date.accessioned2010-09-06T06:02:18Z
 
dc.date.available2010-09-06T06:02:18Z
 
dc.date.issued2009
 
dc.description.abstractReverse transcriptase (RT) of human immunodeficiency virus (HIV)-1 plays a key role in initiating viral replication and is an important target for developing anti-HIV drugs. Our previous study showed that two mutations (Y271A and I274A) in the turn RT (Gln 269-Arg 277) abrogated viral replication, but the replication capacity and RT activity was discordant. In this study, we further investigated why alanine substitutions at these two sites would affect viral replication. We found that both RT activity and RT protein were almost undetectable in viral particles of these two mutants, although the Pr160 gag-pol mutants were properly expressed, transported and incorporated. Using protease inhibition assay, we demonstrated a correlation between the degradation of the RT mutants and the activity of viral protease. Our native gel analysis indicated that the mutations at 271 and 274 amino acids might cause conformational changes, leading to the formation of higher order oligomers instead of dimers, resulting in increased protein instability and susceptibility to viral protease. Thus, residues 271 and 274 are critical to RT stability and resistance to viral protease. The conservation of the two amino acid residues among different strains of HIV-1 lent further support to this conclusion. The knowledge gained here may prove useful in drug design. © 2009 Zhang et al.
 
dc.description.naturepublished_or_final_version
 
dc.identifier.citationPlos One, 2009, v. 4 n. 7 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pone.0006108
 
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0006108
 
dc.identifier.epagee6108
 
dc.identifier.hkuros168240
 
dc.identifier.isiWOS:000267806300001
 
dc.identifier.issn1932-6203
2012 Impact Factor: 3.73
2012 SCImago Journal Rankings: 1.512
 
dc.identifier.issue7
 
dc.identifier.pmcidPMC2701634
 
dc.identifier.pmid19578544
 
dc.identifier.scopuseid_2-s2.0-67650252529
 
dc.identifier.spagee6108
 
dc.identifier.urihttp://hdl.handle.net/10722/68199
 
dc.identifier.volume4
 
dc.languageeng
 
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
 
dc.publisher.placeUnited States
 
dc.relation.ispartofPLoS ONE
 
dc.relation.referencesReferences in Scopus
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.subject.meshAmino Acids - physiology
 
dc.subject.meshDNA Primers
 
dc.subject.meshHIV Reverse Transcriptase - chemistry - genetics
 
dc.subject.meshHIV-1 - enzymology - physiology
 
dc.subject.meshMicroscopy, Fluorescence
 
dc.titleThe Y271 and I274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability
 
dc.typeArticle
 
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<item><contributor.author>Zhang, HJ</contributor.author>
<contributor.author>Wang, YX</contributor.author>
<contributor.author>Wu, H</contributor.author>
<contributor.author>Jin, DY</contributor.author>
<contributor.author>Wen, YM</contributor.author>
<contributor.author>Zheng, BJ</contributor.author>
<date.accessioned>2010-09-06T06:02:18Z</date.accessioned>
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<description.abstract>Reverse transcriptase (RT) of human immunodeficiency virus (HIV)-1 plays a key role in initiating viral replication and is an important target for developing anti-HIV drugs. Our previous study showed that two mutations (Y271A and I274A) in the turn RT (Gln 269-Arg 277) abrogated viral replication, but the replication capacity and RT activity was discordant. In this study, we further investigated why alanine substitutions at these two sites would affect viral replication. We found that both RT activity and RT protein were almost undetectable in viral particles of these two mutants, although the Pr160 gag-pol mutants were properly expressed, transported and incorporated. Using protease inhibition assay, we demonstrated a correlation between the degradation of the RT mutants and the activity of viral protease. Our native gel analysis indicated that the mutations at 271 and 274 amino acids might cause conformational changes, leading to the formation of higher order oligomers instead of dimers, resulting in increased protein instability and susceptibility to viral protease. Thus, residues 271 and 274 are critical to RT stability and resistance to viral protease. The conservation of the two amino acid residues among different strains of HIV-1 lent further support to this conclusion. The knowledge gained here may prove useful in drug design. &#169; 2009 Zhang et al.</description.abstract>
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<subject.mesh>Amino Acids - physiology</subject.mesh>
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Author Affiliations
  1. The University of Hong Kong
  2. Fudan University Shanghai Medical College