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Mechanism of a cytosolic O-glycosyltransferase essential for the synthesis of a bacterial adhesion protein

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
 [1];  [2];  [2];  [2];  [1]
  1. Harvard Medical School, Boston, MA (United States)
  2. San Francisco Veteran Affairs Medical Center, San Francisco, CA (United States); Univ. of California, San Francisco, CA (United States)
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O-glycosylation of Ser and Thr residues is an important process in all organisms, which is only poorly understood. Such modification is required for the export and function of adhesin proteins that mediate the attachment of pathogenic Gram-positive bacteria to host cells. Here, we have analyzed the mechanism by which the cytosolic O-glycosyltransferase GtfA/B of Streptococcus gordonii modifies the Ser/Thr-rich repeats of adhesin. The enzyme is a tetramer containing two molecules each of GtfA and GtfB. The two subunits have the same fold, but only GtfA contains an active site, whereas GtfB provides the primary binding site for adhesin. During a first phase of glycosylation, the conformation of GtfB is restrained by GtfA to bind substrate with unmodified Ser/Thr residues. In a slow second phase, GtfB recognizes residues that are already modified with N-acetylglucosamine, likely by converting into a relaxed conformation in which one interface with GtfA is broken. Here, these results explain how the glycosyltransferase modifies a progressively changing substrate molecule.
Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22). Scientific User Facilities Division
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1241075
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 9 Vol. 113; ISSN 0027-8424
Publisher:
National Academy of SciencesCopyright Statement
Country of Publication:
United States
Language:
ENGLISH

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Cited By (11)

The accessory Sec system (SecY2A2) in Streptococcus pneumoniae is involved in export of pneumolysin toxin, adhesion and biofilm formation journal July 2017
Processivity in Bacterial Glycosyltransferases journal November 2019
Serine-rich repeat proteins from gut microbes journal April 2019
Serine-rich repeat protein adhesins fromLactobacillus reuteridisplay strain specific glycosylation profiles journal November 2018
Structure and Mechanism of Staphylococcus aureus TarS, the Wall Teichoic Acid β-glycosyltransferase Involved in Methicillin Resistance journal December 2016
O-acetylation of the serine-rich repeat glycoprotein GspB is coordinated with accessory Sec transport journal August 2017
Critical Review of Plant Cell Wall Matrix Polysaccharide Glycosyltransferase Activities Verified by Heterologous Protein Expression journal July 2019
How Sweet Are Our Gut Beneficial Bacteria? A Focus on Protein Glycosylation in Lactobacillus journal January 2018
Characterization of the pgf operon involved in the posttranslational modification of Streptococcus mutans surface proteins journal March 2018
Defining the enzymatic pathway for polymorphic O -glycosylation of the pneumococcal serine-rich repeat protein PsrP journal February 2017
Membrane trafficking of the bacterial adhesin GspB and the accessory Sec transport machinery journal December 2018

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
O-glycosylation
Ser/Thr-rich repeats
bacterial adhesin
crystal structure
enzymatic mechanism