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  • Accepted Manuscript: Simulations of cellulose translocation in the bacterial cellulose synthase suggest a regulatory mechanism for the dimeric structure of cellulose

Title: Simulations of cellulose translocation in the bacterial cellulose synthase suggest a regulatory mechanism for the dimeric structure of cellulose

The processive cycle of the bacterial cellulose synthase (Bcs) includes the addition of a single glucose moiety to the end of a growing cellulose chain followed by the translocation of the nascent chain across the plasma membrane. The mechanism of this translocation and its precise location within the processive cycle are not well understood. In particular, the molecular details of how a polymer (cellulose) whose basic structural unit is a dimer (cellobiose) can be constructed by adding one monomer (glucose) at a time are yet to be elucidated. Here, we have utilized molecular dynamics simulations and free energy calculations to the shed light on these questions. We find that translocation forward by one glucose unit is quite favorable energetically, giving a free energy stabilization of greater than 10 kcal mol-1. In addition, there is only a small barrier to translocation, implying that translocation is not rate limiting within the Bcs processive cycle (given experimental rates for cellulose synthesis in vitro). Perhaps most significantly, our results also indicate that steric constraints at the transmembrane tunnel entrance regulate the dimeric structure of cellulose. Namely, when a glucose molecule is added to the cellulose chain in the same orientation as the acceptor glucose,more » the terminal glucose freely rotates upon forward motion, thus suggesting a regulatory mechanism for the dimeric structure of cellulose. We characterize both the conserved and non-conserved enzyme-polysaccharide interactions that drive translocation, and find that 20 of the 25 residues that strongly interact with the translocating cellulose chain in the simulations are well conserved, mostly with polar or aromatic side chains. Our results also allow for a dynamical analysis of the role of the so-called 'finger helix' in cellulose translocation that has been observed structurally. Taken together, these findings aid in the elucidation of the translocation steps of the Bcs processive cycle and may be widely relevant to polysaccharide synthesizing or degrading enzymes that couple catalysis with chain translocation.« less
Authors:
 [1] ;  [1] ;  [1] ;  [2] ;  [1]
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  1. National Renewable Energy Lab. (NREL), Golden, CO (United States)
  2. Univ. of Virginia, Charlottesville, VA (United States)
Publication Date:
Report Number(s):
NREL/JA-5100-65894
Journal ID: ISSN 2041-6520; CSHCBM
Grant/Contract Number:
AC36-08GO28308
Type:
Accepted Manuscript
Journal Name:
Chemical Science
Additional Journal Information:
Journal Volume: 7; Journal Issue: 5; Related Information: Chemical Science; Journal ID: ISSN 2041-6520
Publisher:
Royal Society of Chemistry
Research Org:
National Renewable Energy Lab. (NREL), Golden, CO (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Country of Publication:
United States
Language:
English
Subject:
09 BIOMASS FUELS; 59 BASIC BIOLOGICAL SCIENCES; bacterial cellulose synthase (Bcs); translocation; processive cycle; molecular dynamics simulations
OSTI Identifier:
1250687
Citation Formats
Knott, Brandon C., Crowley, Michael F., Himmel, Michael E., Zimmer, Jochen, and Beckham, Gregg T.. Simulations of cellulose translocation in the bacterial cellulose synthase suggest a regulatory mechanism for the dimeric structure of cellulose. United States: N. p., Web. doi:10.1039/C5SC04558D.
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Knott, Brandon C., Crowley, Michael F., Himmel, Michael E., Zimmer, Jochen, & Beckham, Gregg T.. Simulations of cellulose translocation in the bacterial cellulose synthase suggest a regulatory mechanism for the dimeric structure of cellulose. United States. doi:10.1039/C5SC04558D.
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Knott, Brandon C., Crowley, Michael F., Himmel, Michael E., Zimmer, Jochen, and Beckham, Gregg T.. 2016. "Simulations of cellulose translocation in the bacterial cellulose synthase suggest a regulatory mechanism for the dimeric structure of cellulose". United States. doi:10.1039/C5SC04558D. https://www.osti.gov/servlets/purl/1250687.
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@article{osti_1250687,
title = {Simulations of cellulose translocation in the bacterial cellulose synthase suggest a regulatory mechanism for the dimeric structure of cellulose},
author = {Knott, Brandon C. and Crowley, Michael F. and Himmel, Michael E. and Zimmer, Jochen and Beckham, Gregg T.},
abstractNote = {The processive cycle of the bacterial cellulose synthase (Bcs) includes the addition of a single glucose moiety to the end of a growing cellulose chain followed by the translocation of the nascent chain across the plasma membrane. The mechanism of this translocation and its precise location within the processive cycle are not well understood. In particular, the molecular details of how a polymer (cellulose) whose basic structural unit is a dimer (cellobiose) can be constructed by adding one monomer (glucose) at a time are yet to be elucidated. Here, we have utilized molecular dynamics simulations and free energy calculations to the shed light on these questions. We find that translocation forward by one glucose unit is quite favorable energetically, giving a free energy stabilization of greater than 10 kcal mol-1. In addition, there is only a small barrier to translocation, implying that translocation is not rate limiting within the Bcs processive cycle (given experimental rates for cellulose synthesis in vitro). Perhaps most significantly, our results also indicate that steric constraints at the transmembrane tunnel entrance regulate the dimeric structure of cellulose. Namely, when a glucose molecule is added to the cellulose chain in the same orientation as the acceptor glucose, the terminal glucose freely rotates upon forward motion, thus suggesting a regulatory mechanism for the dimeric structure of cellulose. We characterize both the conserved and non-conserved enzyme-polysaccharide interactions that drive translocation, and find that 20 of the 25 residues that strongly interact with the translocating cellulose chain in the simulations are well conserved, mostly with polar or aromatic side chains. Our results also allow for a dynamical analysis of the role of the so-called 'finger helix' in cellulose translocation that has been observed structurally. Taken together, these findings aid in the elucidation of the translocation steps of the Bcs processive cycle and may be widely relevant to polysaccharide synthesizing or degrading enzymes that couple catalysis with chain translocation.},
doi = {10.1039/C5SC04558D},
journal = {Chemical Science},
number = 5,
volume = 7,
place = {United States},
year = {2016},
month = {1}
}
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Works referenced in this record:

Cell-wall carbohydrates and their modification as a resource for biofuels
journal, May 2008
Scalable molecular dynamics with NAMD
journal, January 2005
  • Phillips, James C.; Braun, Rosemary; Wang, Wei
  • Journal of Computational Chemistry, Vol. 26, Issue 16, p. 1781-1802
  • DOI: 10.1002/jcc.20289

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