scholarly journals Visualizing Conformation Transitions of the Lipid Flippase MurJ

2019 ◽  
Author(s):  
Alvin C. Y. Kuk ◽  
Aili Hao ◽  
Ziqiang Guan ◽  
Seok-Yong Lee
Keyword(s):  
Mass Spectrometry ◽  
Cell Wall ◽  
Bacterial Cell ◽  
Structural Information ◽  
Conformational Transitions ◽  
Cell Wall Synthesis ◽  
Lipid Ii ◽  
Bacterial Peptidoglycan ◽  
Lipid Flippase ◽  
Conformation Transitions

AbstractThe biosynthesis of many polysaccharides, including bacterial peptidoglycan and eukaryotic N-linked glycans, requires transport of lipid-linked oligosaccharide (LLO) precursors across the membrane by specialized flippases. MurJ is the flippase for the lipid-linked peptidoglycan precursor Lipid II, a key player in bacterial cell wall synthesis, and a target of recently discovered antibacterials. However, the flipping mechanism of LLOs including Lipid II remains poorly understood due to a dearth of structural information. Here we report crystal structures of MurJ captured in inward-closed, inward-open, inward-occluded and outward-facing conformations. Together with cysteine accessibility, mass spectrometry, and complementation studies, we elucidate the conformational transitions in MurJ that mediate lipid flipping, identified the key ion for function, and provide a framework for the development of inhibitors.

scholarly journals Lipid Intermediates in the Biosynthesis of Bacterial Peptidoglycan

2007 ◽  
Vol 71 (4) ◽  
pp. 620-635 ◽  
Author(s):  
Jean van Heijenoort
Keyword(s):  
Cell Wall ◽  
Bacterial Cell ◽  
Cytoplasmic Membrane ◽  
Monomer Unit ◽  
Mechanisms Of Action ◽  
Lipid Ii ◽  
Glycan Chain ◽  
Bacterial Peptidoglycan ◽  
Modified Forms ◽  
Enzymatic Methods

SUMMARY This review is an attempt to bring together and critically evaluate the now-abundant but dispersed data concerning the lipid intermediates of the biosynthesis of bacterial peptidoglycan. Lipid I, lipid II, and their modified forms play a key role not only as the specific link between the intracellular synthesis of the peptidoglycan monomer unit and the extracytoplasmic polymerization reactions but also in the attachment of proteins to the bacterial cell wall and in the mechanisms of action of antibiotics with which they form specific complexes. The survey deals first with their detection, purification, structure, and preparation by chemical and enzymatic methods. The recent important advances in the study of transferases MraY and MurG, responsible for the formation of lipids I and II, are reported. Various modifications undergone by lipids I and II are described, especially those occurring in gram-positive organisms. The following section concerns the cellular location of the lipid intermediates and the translocation of lipid II across the cytoplasmic membrane. The great efforts made since 2000 in the study of the glycosyltransferases catalyzing the glycan chain formation with lipid II or analogues are analyzed in detail. Finally, examples of antibiotics forming complexes with the lipid intermediates are presented.

scholarly journals The ColM Family, Polymorphic Toxins Breaching the Bacterial Cell Wall

mBio ◽  
2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Maarten G. K. Ghequire ◽  
Susan K. Buchanan ◽  
René De Mot
Keyword(s):  
Cell Wall ◽  
Bacterial Cell ◽  
Cytoplasmic Membrane ◽  
Catalytic Domain ◽  
Gram Negative Bacteria ◽  
Antibacterial Peptides ◽  
Gram Negative ◽  
Lipid Ii ◽  
Associated Proteins ◽  
Colicin M

ABSTRACT Bacteria host an arsenal of antagonism-mediating molecules to combat for ecologic space. Bacteriocins represent a pivotal group of secreted antibacterial peptides and proteins assisting in this fight, mainly eliminating relatives. Colicin M, a model for peptidoglycan-interfering bacteriocins in Gram-negative bacteria, appears to be part of a set of polymorphic toxins equipped with such a catalytic domain (ColM) targeting lipid II. Diversifying recombination has enabled parasitism of different receptors and has also given rise to hybrid bacteriocins in which ColM is associated with another toxin module. Remarkably, ColM toxins have recruited a diverse array of immunity partners, comprising cytoplasmic membrane-associated proteins with different topologies. Together, these findings suggest that different immunity mechanisms have evolved for ColM, in contrast to bacteriocins with nuclease activities.

scholarly journals Lipid Flippases for Bacterial Peptidoglycan Biosynthesis

2015 ◽  
Vol 8s1 ◽  
pp. LPI.S31783 ◽  
Author(s):  
Natividad Ruiz
Keyword(s):  
Cell Wall ◽  
The Body ◽  
Cellular Compartment ◽  
Peptidoglycan Biosynthesis ◽  
Lipid Ii ◽  
Common Strategy ◽  
Nucleotide Sugars ◽  
Membrane Bound ◽  
The Subject ◽  
Bacterial Peptidoglycan

The biosynthesis of cellular polysaccharides and glycoconjugates often involves lipid-linked intermediates that need to be translocated across membranes. Essential pathways such as N-glycosylation in eukaryotes and biogenesis of the peptidoglycan (PG) cell wall in bacteria share a common strategy where nucleotide-sugars are used to build a membrane-bound oligosaccharide precursor that is linked to a phosphorylated isoprenoid lipid. Once made, these lipid-linked intermediates must be translocated across a membrane so that they can serve as substrates in a different cellular compartment. How translocation occurs is poorly understood, although it clearly requires a transporter or flippase. Identification of these transporters is notoriously difficult, and, in particular, the identity of the flippase of lipid II, an intermediate required for PG biogenesis, has been the subject of much debate. Here, I will review the body of work that has recently fueled this controversy, centered on proposed flippase candidates FtsW, MurJ, and AmJ.

scholarly journals Molecular architecture of the PBP2–MreC core bacterial cell wall synthesis complex

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Carlos Contreras-Martel ◽  
Alexandre Martins ◽  
Chantal Ecobichon ◽  
Daniel Maragno Trindade ◽  
Pierre-Jean Matteï ◽  
...  
Keyword(s):  
Cell Wall ◽  
Bacterial Cell ◽  
Bacterial Cell Wall ◽  
Molecular Architecture ◽  
Cell Wall Synthesis
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