Publication Date:
2007-07-28
Description:
NS3, an essential helicase for replication of hepatitis C virus, is a model enzyme for investigating helicase function. Using single-molecule fluorescence analysis, we showed that NS3 unwinds DNA in discrete steps of about three base pairs (bp). Dwell time analysis indicated that about three hidden steps are required before a 3-bp step is taken. Taking into account the available structural data, we propose a spring-loaded mechanism in which several steps of one nucleotide per adenosine triphosphate molecule accumulate tension on the protein-DNA complex, which is relieved periodically via a burst of 3-bp unwinding. NS3 appears to shelter the displaced strand during unwinding, and, upon encountering a barrier or after unwinding 〉18 bp, it snaps or slips backward rapidly and repeats unwinding many times in succession. Such repetitive unwinding behavior over a short stretch of duplex may help to keep secondary structures resolved during viral genome replication.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3565428/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3565428/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Myong, Sua -- Bruno, Michael M -- Pyle, Anna M -- Ha, Taekjip -- R01 GM060620/GM/NIGMS NIH HHS/ -- R01 GM065367/GM/NIGMS NIH HHS/ -- R01-GM060620/GM/NIGMS NIH HHS/ -- R01-GM065367/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2007 Jul 27;317(5837):513-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Physics Department, University of Illinois, 1110 West Green Street, Urbana, IL 61801, USA. smyong@uiuc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17656723" target="_blank"〉PubMed〈/a〉
Keywords:
Adenosine Triphosphate/metabolism
;
Base Pairing
;
DNA/chemistry/*metabolism
;
DNA Helicases/*metabolism
;
Fluorescence Resonance Energy Transfer
;
Hepacivirus/*enzymology
;
Models, Biological
;
Models, Molecular
;
Nucleic Acid Conformation
;
Temperature
;
Viral Nonstructural Proteins/chemistry/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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