Research article summary (published 18 Oct 2009):

Molecular mechanism for lateral lipid diffusion between the outer membrane external leaflet and a beta-barrel hydrocarbon ruler.

Full Abstract

Membrane-intrinsic enzymes are embedded in lipids, yet how such enzymes interrogate lipid substrates remains a largely unexplored fundamental question. The outer membrane phospholipid:lipid A palmitoyltransferase PagP combats host immune defenses during infection and selects a palmitate chain using its beta-barrel interior hydrocarbon ruler. Both a molecular embrasure and crenel in Escherichia coli PagP display weakened transmembrane beta-strand hydrogen bonding to provide potential lateral routes for diffusion of the palmitoyl group between the hydrocarbon ruler and outer membrane external leaflet. Prolines in strands A and B lie beneath the dynamic L1 surface loop flanking the embrasure, whereas the crenel is flanked by prolines in strands F and G. Reversibly barricading the embrasure prevents lipid A palmitoylation without affecting the slower phospholipase reaction. Lys42Ala PagP is also a dedicated phospholipase, implicating this disordered L1 loop residue in lipid A recognition. The embrasure barricade additionally prevents palmitoylation of nonspecific fatty alcohols, but not miscible alcohols. Irreversibly barricading the crenel inhibits both lipid A palmitoylation and phospholipase reactions without compromising PagP structure. These findings indicate lateral palmitoyl group diffusion within the PagP hydrocarbon ruler is likely gated during phospholipid entry via the crenel and during lipid A egress via the embrasure.

Author information

Author/s: Khan, M Adil (MA); Bishop, Russell E (RE);

Affiliation: Department of Biochemistry and Biomedical Sciences and Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada L8N 3Z5.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Biochemistry (Biochemistry), published in United States. (Language: eng)

Reference: 2009-Oct; vol 48 (issue 41) : pp 9745-56

Dates: Created 2009/10/13; Completed 2009/11/02;

PMID: 19769329, status: MEDLINE (last retrieval date: 11/2/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Acyltransferases - chemistry; genetics Alkylation Bacterial Outer Membrane Proteins - chemistry; genetics Bicyclo Compounds - metabolism DNA Primers Diffusion Escherichia coli - metabolism Escherichia coli Proteins - chemistry; genetics

Lipids - chemistry Models, Molecular Mutagenesis, Site-Directed Palmitic Acid - chemistry; metabolism Phenanthrolines - metabolism Phospholipids - biosynthesis Protein Conformation Protein Subunits - chemistry

Associated Chemicals: Bacterial Outer Membrane Proteins (0) ; Bicyclo Compounds (0) ; DNA Primers (0) ; Escherichia coli Proteins (0) ; Lipids (0) ; Phenanthrolines (0) ; Phospholipids (0) ; Protein Subunits (0) ; Palmitic Acid (57-10-3) ; dibromobimane (68654-25-1) ; Acyltransferases (EC 2.3.-) ; PagP protein, E coli (EC 2.3.1.-)

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