Single-Base Pair Unwinding and Asynchronous RNA Release by the Hepatitis C Virus NS3 Helicase

被引：106

作者：

Cheng, Wei ^{[1
]}

Arunajadai, Srikesh G. ^{[2
]}

Moffitt, Jeffrey R. ^{[3
]}

Tinoco, Ignacio, Jr. ^{[4
]}

Bustamante, Carlos ^{[4
,5
,6
,7
]}

机构：

[1] Univ Michigan, Coll Pharm, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA

[2] Columbia Univ, Dept Biostat, New York, NY 10032 USA

[3] Harvard Univ, Ctr Syst Biol, Cambridge, MA 02138 USA

[4] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA

[5] Univ Calif Berkeley, Inst QB3, Berkeley, CA 94720 USA

[6] Univ Calif Berkeley, Jason L Choy Lab Single Mol Biophys, Dept Mol & Cellular Biol, Dept Phys, Berkeley, CA 94720 USA

[7] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA

来源：

SCIENCE | 2011年 / 333卷 / 6050期

关键词：

DNA HELICASES; MECHANISM; TRANSLOCATION; REVEAL; UVRD; RESOLUTION; DYNAMICS; MOLECULE; MONOMER; ATP;

D O I：

10.1126/science.1206023

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Nonhexameric helicases use adenosine triphosphate (ATP) to unzip base pairs in double-stranded nucleic acids (dsNAs). Studies have suggested that these helicases unzip dsNAs in single-base pair increments, consuming one ATP molecule per base pair, but direct evidence for this mechanism is lacking. We used optical tweezers to follow the unwinding of double-stranded RNA by the hepatitis C virus NS3 helicase. Single-base pair steps by NS3 were observed, along with nascent nucleotide release that was asynchronous with base pair opening. Asynchronous release of nascent nucleotides rationalizes various observations of its dsNA unwinding and may be used to coordinate the translocation speed of NS3 along the RNA during viral replication.

引用

页码：1746 / 1749

页数：4

共 28 条

[1] Visualizing ATP-Dependent RNA Translocation by the NS3 Helicase from HCV [J].

Appleby, Todd C. ;

Anderson, Robert ;

Fedorova, Olga ;

Pyle, Anna M. ;

Wang, Ruth ;

Liu, Xiaohong ;

Brendza, Katherine M. ;

Somoza, John R. .

JOURNAL OF MOLECULAR BIOLOGY, 2011, 405 (05) :1139-1153

[2] A point process driven multiple change point model: A robust resistant approach [J].

Arunajadai, Srikesh G. .

MATHEMATICAL BIOSCIENCES, 2009, 220 (01) :57-71

[3] ENTROPIC ELASTICITY OF LAMBDA-PHAGE DNA [J].

BUSTAMANTE, C ;

MARKO, JF ;

SIGGIA, ED ;

SMITH, S .

SCIENCE, 1994, 265 (5178) :1599-1600

[4] NS3 helicase actively separates RNA strands and senses sequence barriers ahead of the opening fork [J].

Cheng, Wei ;

Dumont, Sophie ;

Tinoco, Ignacio, Jr. ;

Bustamante, Carlos .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (35) :13954-13959

[5] Use of tapered amplifier diode laser for biological-friendly high-resolution optical trapping [J].

Cheng, Wei ;

Hou, Ximiao ;

Ye, Fangmao .

OPTICS LETTERS, 2010, 35 (17) :2988-2990

[6] Single-molecule assay reveals strand switching and enhanced processivity of UvrD [J].

Dessinges, MN ;

Lionnet, T ;

Xi, XG ;

Bensimon, D ;

Croquette, V .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (17) :6439-6444

[7] Nucleic acid unwinding by hepatitis C virus and bacteriophage T7 helicases is sensitive to base pair stability [J].

Donmez, Ilker ;

Rajagopal, Vaishnavi ;

Jeong, Yong-Joo ;

Patel, Smita S. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (29) :21116-21123

[8] RNA translocation and unwinding mechanism of HCVNS3 helicase and its coordination by ATP [J].

Dumont, S ;

Cheng, W ;

Serebrov, V ;

Beran, RK ;

Tinoco, I ;

Pyle, AM ;

Bustamante, C .

NATURE, 2006, 439 (7072) :105-108

[9] Intermediates revealed in the kinetic mechanism for DNA unwinding by a monomeric helicase [J].

Eoff, RL ;

Raney, KD .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2006, 13 (03) :242-249

[10] Three conformational snapshots of the hepatitis C virus NS3 helicase reveal a ratchet translocation mechanism [J].

Gu, Meigang ;

Rice, Charles M. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (02) :521-528

← 1 2 3 →