A bifunctional O-antigen polymerase structure reveals a new glycosyltransferase family

Nature Chemical Biology
Bradley R ClarkeChris Whitfield

Abstract

Lipopolysaccharide O-antigen is an attractive candidate for immunotherapeutic strategies targeting antibiotic-resistant Klebsiella pneumoniae. Several K. pneumoniae O-serotypes are based on a shared O2a-antigen backbone repeating unit: (→ 3)-α-Galp-(1 → 3)-β-Galf-(1 →). O2a antigen is synthesized on undecaprenol diphosphate in a pathway involving the O2a polymerase, WbbM, before its export by an ATP-binding cassette transporter. This dual domain polymerase possesses a C-terminal galactopyranosyltransferase resembling known GT8 family enzymes, and an N-terminal DUF4422 domain identified here as a galactofuranosyltransferase defining a previously unrecognized family (GT111). Functional assignment of DUF4422 explains how galactofuranose is incorporated into various polysaccharides of importance in vaccine production and the food industry. In the 2.1-Å resolution structure, three WbbM protomers associate to form a flattened triangular prism connected to a central stalk that orients the active sites toward the membrane. The biochemical, structural and topological properties of WbbM offer broader insight into the mechanisms of assembly of bacterial cell-surface glycans.

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Citations

Jun 23, 2020·Annual Review of Biochemistry·Christopher A CaffaletteJochen Zimmer
May 20, 2020·The Journal of Biological Chemistry·Chris WhitfieldSteven D Kelly
Jan 12, 2021·Current Opinion in Structural Biology·Sean D Liston, Lisa M Willis
Dec 19, 2020·FEMS Microbiology Reviews·Tong SuLok-To Sham
Nov 4, 2020·Proceedings of the National Academy of Sciences of the United States of America·Immacolata SpecialeCristina De Castro
Apr 22, 2021·Proceedings of the National Academy of Sciences of the United States of America·Karin SavkováKatarína Mikušová
Sep 4, 2021·Infectious Diseases and Therapy·Lucas AssoniMichelle Darrieux

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Datasets Mentioned

BETA
L31762

Methods Mentioned

BETA
nuclear magnetic resonance
glycosylation
two-hybrid
size exclusion chromatography
pull-down
PCR
protein assay
NMR

Software Mentioned

Phenix autosol
MAFFT
tblastn
PrDOS
PISA
KfoC
Phenix
Heliquest
ESPript
PhyML

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