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  Molecular Mechanism of Processive 3 ' to 5 ' RNA Translocation in the Active Subunit of the RNA Exosome Complex

Vukovic, L., Chipot, C., Makino, D. L., Conti, E., & Schulten, K. (2016). Molecular Mechanism of Processive 3 ' to 5 ' RNA Translocation in the Active Subunit of the RNA Exosome Complex. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 138(12), 4069-4078. doi:10.1021/jacs.5b12065.

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 Creators:
Vukovic, Lela1, Author
Chipot, Christophe1, Author
Makino, Debora L.2, Author           
Conti, Elena2, Author           
Schulten, Klaus1, Author
Affiliations:
1external, ou_persistent22              
2Conti, Elena / Structural Cell Biology, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565144              

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Free keywords: DYNAMICS SIMULATIONS; QUALITY-CONTROL; FREE-ENERGIES; DEGRADATION; MULTIPLE; EXORIBONUCLEASE; PATHWAYS; CHANNEL; MOTOR; WATER
 Abstract: Recent experimental studies revealed structural details of 3' to 5' degradation of RNA molecules, performed by the exosome complex. ssRNA is channeled through its multi subunit ring-like core into the active site tunnel of its key exonuclease subunit Rrp44, which acts both as an enzyme and a motor. Even in isolation, Rrp44 can pull and sequentially cleave RNA nucleotides, one at a time, without any external energy input and release a final 3-5 nucleotide long product. Using molecular dynamics simulations, we identify the main factors that control these processes. Our free energy calculations reveal that RNA transfer from solution into the active site of Rrp44 is highly favorable, but dependent on the length of the RNA strand. While RNA strands formed by 5 nucleotides or more correspond to a decreasing free energy along the translocation coordinate toward the cleavage site, a 4-nucleotide RNA experiences a free energy barrier along the same direction, potentially leading to incomplete cleavage of ssRNA and the release of short (3-5) nucleotide products. We provide new insight into how Rrp44 catalyzes a localized enzymatic reaction and performs an action distributed over several RNA nucleotides, leading eventually to the translocation of whole RNA segments into the position suitable for cleavage.

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Language(s): eng - English
 Dates: 2016
 Publication Status: Published in print
 Pages: 10
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000373518800027
DOI: 10.1021/jacs.5b12065
 Degree: -

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Title: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Source Genre: Journal
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Publ. Info: 1155 16TH ST, NW, WASHINGTON, DC 20036 USA : AMER CHEMICAL SOC
Pages: - Volume / Issue: 138 (12) Sequence Number: - Start / End Page: 4069 - 4078 Identifier: ISSN: 0002-7863