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Title: The LINKS motif zippers trans-acyltransferase polyketide synthase assembly lines into a biosynthetic megacomplex

Abstract

Polyketides such as the clinically-valuable antibacterial agent mupirocin are constructed by architecturally-sophisticated assembly lines known as trans-acyltransferase polyketide synthases. Organelle-sized megacomplexes composed of several copies of trans-acyltransferase polyketide synthase assembly lines have been observed by others through transmission electron microscopy to be located at the Bacillus subtilis plasma membrane, where the synthesis and export of the antibacterial polyketide bacillaene takes place. In this work we analyze ten crystal structures of trans-acyltransferase polyketide synthases ketosynthase domains, seven of which are reported here for the first time, to characterize a motif capable of zippering assembly lines into a megacomplex. While each of the three-helix LINKS (Laterally-INteracting Ketosynthase Sequence) motifs is observed to similarly dock with a spatially-reversed copy of itself through hydrophobic and ionic interactions, the amino acid sequences of this motif are not conserved. Such a code is appropriate for mediating homotypic contacts between assembly lines to ensure the ordered self-assembly of a noncovalent, yet tightly-knit, enzymatic network. Furthermore, LINKS-mediated lateral interactions would also have the effect of bolstering the vertical association of the polypeptides that comprise a polyketide synthase assembly line.

Authors:
 [1];  [1];  [1];  [1];  [1];  [1]
  1. Univ. of Texas, Austin, TX (United States)
Publication Date:
Research Org.:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division; National Institutes of Health (NIH); Welch Foundation
OSTI Identifier:
1357643
Alternate Identifier(s):
OSTI ID: 1400020
Grant/Contract Number:  
AC02-05CH11231; AC02-06CH11357; GM106112; F-1712
Resource Type:
Accepted Manuscript
Journal Name:
Journal of Structural Biology
Additional Journal Information:
Journal Volume: 193; Journal Issue: 3; Journal ID: ISSN 1047-8477
Publisher:
Elsevier
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; Modular polyketide synthase; Megacomplex; Protein–protein interaction; X-ray crystallography

Citation Formats

Gay, Darren C., Wagner, Drew T., Meinke, Jessica L., Zogzas, Charles E., Gay, Glen R., and Keatinge-Clay, Adrian T. The LINKS motif zippers trans-acyltransferase polyketide synthase assembly lines into a biosynthetic megacomplex. United States: N. p., 2015. Web. doi:10.1016/j.jsb.2015.12.011.
Gay, Darren C., Wagner, Drew T., Meinke, Jessica L., Zogzas, Charles E., Gay, Glen R., & Keatinge-Clay, Adrian T. The LINKS motif zippers trans-acyltransferase polyketide synthase assembly lines into a biosynthetic megacomplex. United States. https://doi.org/10.1016/j.jsb.2015.12.011
Gay, Darren C., Wagner, Drew T., Meinke, Jessica L., Zogzas, Charles E., Gay, Glen R., and Keatinge-Clay, Adrian T. Wed . "The LINKS motif zippers trans-acyltransferase polyketide synthase assembly lines into a biosynthetic megacomplex". United States. https://doi.org/10.1016/j.jsb.2015.12.011. https://www.osti.gov/servlets/purl/1357643.
@article{osti_1357643,
title = {The LINKS motif zippers trans-acyltransferase polyketide synthase assembly lines into a biosynthetic megacomplex},
author = {Gay, Darren C. and Wagner, Drew T. and Meinke, Jessica L. and Zogzas, Charles E. and Gay, Glen R. and Keatinge-Clay, Adrian T.},
abstractNote = {Polyketides such as the clinically-valuable antibacterial agent mupirocin are constructed by architecturally-sophisticated assembly lines known as trans-acyltransferase polyketide synthases. Organelle-sized megacomplexes composed of several copies of trans-acyltransferase polyketide synthase assembly lines have been observed by others through transmission electron microscopy to be located at the Bacillus subtilis plasma membrane, where the synthesis and export of the antibacterial polyketide bacillaene takes place. In this work we analyze ten crystal structures of trans-acyltransferase polyketide synthases ketosynthase domains, seven of which are reported here for the first time, to characterize a motif capable of zippering assembly lines into a megacomplex. While each of the three-helix LINKS (Laterally-INteracting Ketosynthase Sequence) motifs is observed to similarly dock with a spatially-reversed copy of itself through hydrophobic and ionic interactions, the amino acid sequences of this motif are not conserved. Such a code is appropriate for mediating homotypic contacts between assembly lines to ensure the ordered self-assembly of a noncovalent, yet tightly-knit, enzymatic network. Furthermore, LINKS-mediated lateral interactions would also have the effect of bolstering the vertical association of the polypeptides that comprise a polyketide synthase assembly line.},
doi = {10.1016/j.jsb.2015.12.011},
journal = {Journal of Structural Biology},
number = 3,
volume = 193,
place = {United States},
year = {Wed Dec 23 00:00:00 EST 2015},
month = {Wed Dec 23 00:00:00 EST 2015}
}

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Cited by: 17 works
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