Function of Escherichia coli MsbA, an Essential ABC Family Transporter, in Lipid A and Phospholipid Biosynthesis

Zhou, Zhimin; White, Kimberly A.; Polissi, Alessandra; Georgopoulos, Costa; Raetz, Christian R. H.

doi:10.1074/jbc.273.20.12466

Cited by 326 publications

(352 citation statements)

References 46 publications

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“…Of the five ABC transporters of the exporter fold crystallized to date only bacterial MsbA and P-glycoprotein (ABCB1) have been shown to transport lipidic substrates. Depletion of cellular MsbA or the presence of a conditionally inactivating mutation in this protein result in loss of lipid A and phospholipid transport from the cytoplasmic to the outer membrane in bacterial cells, suggesting a general flippase function for MsbA [87,88]. This evidence is confirmed by reconstitution experiments, in which MsbA has been shown to translocate a wide variety of fluorescent-labeled phospholipids, albeit with low activity [72].…”

Section: Putative Catalytic Mechanism Of Abc Transporters Of the "Expmentioning

confidence: 71%

Structure and mechanism of ATP-dependent phospholipid transporters

López‐Marqués

Poulsen

Bailly

et al. 2015

Biochimica et Biophysica Acta (BBA) - General Subjects

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Background: ATP-binding cassette (ABC) transporters and P4-ATPases are two large and seemingly unrelated families of primary active pumps involved in moving phospholipids from one leaflet of a biological membrane to the other. Scope of review: This review aims to identify common mechanistic features in the way phospholipid flipping is carried out by two evolutionarily unrelated families of transporters. Major conclusions: Both protein families hydrolyze ATP, although they employ different mechanisms to use it, and have a comparable size with twelve transmembrane segments in the functional unit. Further, despite differences in overall architecture, both appear to operate by an alternating access mechanism and during transport they might allow access of phospholipids to the internal part of the transmembrane domain. The latter feature is obvious for ABC transporters, but phospholipids and other hydrophobic molecules have also been found embedded in P-type ATPase crystal structures. Taken together, in two diverse groups of pumps, nature appears to have evolved quite similar ways of flipping phospholipids. General significance: Our understanding of the structural basis for phospholipid flipping is still limited but it seems plausible that a general mechanism for phospholipid flipping exists in nature. This article is part of a Special Issue entitled Structural biochemistry and biophysics of membrane proteins.

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Section: Putative Catalytic Mechanism Of Abc Transporters Of the "Expmentioning

confidence: 71%

Structure and mechanism of ATP-dependent phospholipid transporters

López‐Marqués

Poulsen

Bailly

et al. 2015

Biochimica et Biophysica Acta (BBA) - General Subjects

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“…Besides the ABC-transporter and Wzy-dependent export mechanisms, a third mechanism involving the ABC-transporter protein MsbA has been proposed to mediate the export of nascent lipopolysaccharide (LPS) molecules consisting of the lipid A and core components (47). A MsbA-like protein encoded by the S. meliloti ndvA gene is involved in the export of ␤-glucan (48).…”

Section: Resultsmentioning

confidence: 99%

The complete sequence of the 1,683-kb pSymB megaplasmid from the N ₂ -fixing endosymbiont Sinorhizobium meliloti

Finan

Weidner

Wong

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

286

228

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Analysis of the 1,683,333-nt sequence of the pSymB megaplasmid from the symbiotic N2-fixing bacterium Sinorhizobium meliloti revealed that the replicon has a high gene density with a total of 1,570 protein-coding regions, with few insertion elements and regions duplicated elsewhere in the genome. The only copies of an essential arg-tRNA gene and the minCDE genes are located on pSymB. Almost 20% of the pSymB sequence carries genes encoding solute uptake systems, most of which were of the ATP-binding cassette family. Many previously unsuspected genes involved in polysaccharide biosynthesis were identified and these, together with the two known distinct exopolysaccharide synthesis gene clusters, show that 14% of the pSymB sequence is dedicated to polysaccharide synthesis. Other recognizable gene clusters include many involved in catabolic activities such as protocatechuate utilization and phosphonate degradation. The functions of these genes are consistent with the notion that pSymB plays a major role in the saprophytic competence of the bacteria in the soil environment.A mong the bacteria, the ␣-proteobacteria appear unusual because of the presence of multiple replicons within the same bacterial strain (1). In the case of Agrobacterium tumefaciens, the causative agent of crown gall disease, the genome contains both a linear and a circular chromosome (2). Many (but not all) of the bacteria that form N 2 -fixing root nodules on leguminous plants are characterized by the presence of multiple plasmids greater than 400 kb in size. In the case of the N 2 -fixing symbiont Sinorhizobium meliloti, there are three replicons, a 3,654-kb circular chromosome (3, 4) and two megaplasmids 1,354 and 1,683 kb in size (5-7). The smaller of the megaplasmids, variously called pSymA, pNod-Nif, or pRmeSU47a, is known to carry many of the genes involved in root nodule formation (nod) and nitrogen fixation (nif ) (8, 9).The 1,683-kb megaplasmid, referred to as pSymB, pExo, or pRmeSU47b, is known to carry various gene clusters involved in exopolysaccharide (EPS) synthesis, C 4 -dicarboxylate transport, and lactose metabolism (10-12). Early studies focused on mutations that abolished synthesis of the succinoglycan EPS, EPS I, because these mutations resulted in a loss of the ability to form normal N 2 -fixing root nodules. This symbiotic defect was rescued by second-site mutations that increased the synthesis of a second galactoglucan EPS (EPS II), whose biosynthetic genes were also located on the pSymB megaplasmid (13,14). Other genes located on pSymB that are required for the formation of N 2 -fixing root nodules include the C 4 -dicarboxylate (dctA) and phosphate transport (phoCDET) genes and the bacA gene (15-18). The presence of large plasmids in bacteria that form associations with plants was described over 20 years ago (19). However, with the exception of the symbiotic genes in relatively small regions of these plasmids, the broader biological role of the plasmids in the biology of the organism has remained obscure. We constructed a ...

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“…Bacterial GPL are synthesized on the inner leaflet of the IM by defined biosynthetic mechanisms (16). However, unlike lipid A, which is enzymatically flipped and transported to the OM by specialized protein machinery (17), our current understanding of the mechanism of GPL transport to the OM remains rudimentary by comparison (12), and specific regulation of OM GPL has not been demonstrated. Therefore, we explored the hypothesis that the S. Typhimurium PhoPQ virulence system regulates OM GPL content.…”

Section: Significancementioning

confidence: 99%

PhoPQ regulates acidic glycerophospholipid content of the Salmonella Typhimurium outer membrane

Dalebroux¹,

Matamouros²,

Whittington

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

141

172

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Significance The outer membrane (OM) of Gram-negative bacteria is composed of lipopolysaccharide (LPS) and glycerophospholipids (GPLs). Environmental regulation of LPS promotes bacterial resistance to host cationic antimicrobial peptides by altering surface charge and hydrophobicity. This work demonstrates that pathogenic Salmonella coordinately regulate GPL and LPS through the PhoPQ regulatory proteins and the OM palmitoyltransferase enzyme PagP. The broad conservation of PhoPQ and PagP in bacteria suggests that environmental regulation of OM GPL may be a conserved stress-response strategy for antimicrobial resistance. Improved understanding of OM GPL synthesis, transport, and modification could lead to new therapies that target the bacterial OM barrier.

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Function of Escherichia coli MsbA, an Essential ABC Family Transporter, in Lipid A and Phospholipid Biosynthesis

Abstract: The Escherichia coli msbA gene, first identified as a multicopy suppressor of htrB mutations, has been proposed to transport nascent core-lipid A molecules across the inner membrane (Polissi, A., and Georgopoulos, C.

Cited by 326 publications

References 46 publications

Structure and mechanism of ATP-dependent phospholipid transporters

Structure and mechanism of ATP-dependent phospholipid transporters

The complete sequence of the 1,683-kb pSymB megaplasmid from the N ₂ -fixing endosymbiont Sinorhizobium meliloti

PhoPQ regulates acidic glycerophospholipid content of the Salmonella Typhimurium outer membrane

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Function of Escherichia coli MsbA, an Essential ABC Family Transporter, in Lipid A and Phospholipid Biosynthesis

Abstract: The Escherichia coli msbA gene, first identified as a multicopy suppressor of htrB mutations, has been proposed to transport nascent core-lipid A molecules across the inner membrane (Polissi, A., and Georgopoulos, C.

Cited by 326 publications

References 46 publications

Structure and mechanism of ATP-dependent phospholipid transporters

Structure and mechanism of ATP-dependent phospholipid transporters

The complete sequence of the 1,683-kb pSymB megaplasmid from the N 2 -fixing endosymbiont Sinorhizobium meliloti

PhoPQ regulates acidic glycerophospholipid content of the Salmonella Typhimurium outer membrane

Contact Info

Product

Resources

About

The complete sequence of the 1,683-kb pSymB megaplasmid from the N ₂ -fixing endosymbiont Sinorhizobium meliloti