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PMID:11013210

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Citation

Bishop, RE, Gibbons, HS, Guina, T, Trent, MS, Miller, SI and Raetz, CR (2000) Transfer of palmitate from phospholipids to lipid A in outer membranes of gram-negative bacteria. EMBO J. 19:5071-80

Abstract

Regulated covalent modifications of lipid A are implicated in virulence of pathogenic Gram-negative bacteria. The Salmonella typhimurium PhoP/PhoQ-activated gene pagP is required both for biosynthesis of hepta-acylated lipid A species containing palmitate and for resistance to cationic anti-microbial peptides. Palmitoylated lipid A can also function as an endotoxin antagonist. We now show that pagP and its Escherichia coli homolog (crcA) encode an unusual enzyme of lipid A biosynthesis localized in the outer membrane. PagP transfers a palmitate residue from the sn-1 position of a phospholipid to the N-linked hydroxymyristate on the proximal unit of lipid A (or its precursors). PagP bearing a C-terminal His(6)-tag accumulated in outer membranes during overproduction, was purified with full activity and was shown by cross-linking to behave as a homodimer. PagP is the first example of an outer membrane enzyme involved in lipid A biosynthesis. Additional pagP homologs are encoded in the genomes of Yersinia and Bordetella species. PagP may provide an adaptive response toward both Mg(2+) limitation and host innate immune defenses.

Links

PubMed PMC302101 Online version:10.1093/emboj/19.19.5071

Keywords

Acylation; Acyltransferases/genetics; Acyltransferases/isolation & purification; Acyltransferases/metabolism; Animals; Bacterial Outer Membrane Proteins/genetics; Bacterial Outer Membrane Proteins/isolation & purification; Bacterial Outer Membrane Proteins/metabolism; Bacterial Proteins/metabolism; Carbohydrate Sequence; Cell Membrane; Electrophoresis, Polyacrylamide Gel; Escherichia coli/genetics; Escherichia coli/metabolism; Lipid A/biosynthesis; Lipid A/metabolism; Molecular Sequence Data; Palmitates/metabolism; Phospholipids/metabolism; Salmonella typhimurium/enzymology; Salmonella typhimurium/genetics; Salmonella typhimurium/metabolism; Sequence Homology, Amino Acid

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

ECOLI:PAGP

enables

GO:0016416: O-palmitoyltransferase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

ECOLI:PAGP

involved_in

GO:0009245: lipid A biosynthetic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

ECOLI:PAGP

located_in

GO:0009279: cell outer membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

ECOLI:PAGP

acts_upstream_of_or_within

GO:0009245: lipid A biosynthetic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

SALTY:PAGP

enables

GO:0016409: palmitoyltransferase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

SALTY:PAGP

involved_in

GO:0009245: lipid A biosynthetic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

SALTY:PAGP

located_in

GO:0009279: cell outer membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

SALTY:Q9ZHL7

involved_in

GO:0009245: lipid A biosynthetic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

SALTY:Q9ZHL7

part_of

GO:0009279: cell outer membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

SALTY:Q9ZHL7

enables

GO:0016409: palmitoyltransferase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

See also

References

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