How to move an amphipathic molecule across a lipid bilayer: different mechanisms for different ABC transporters?
| Autor: | David J. Carrier, Alison Baker, Frederica L. Theodoulou, Theresia A. Schaedler, Stephen A. Baldwin |
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| Rok vydání: | 2016 |
| Předmět: |
Lipopolysaccharides
0301 basic medicine Lipid Bilayers mechanism ATP-binding cassette transporter Biology Biochemistry Membrane Proteins From A to Z 03 medical and health sciences Acyl-CoA chemistry.chemical_compound Thioesterase Coenzyme A Ligases Peroxisomes Animals Humans peroxisome Lipid bilayer chemistry.chemical_classification Bacteria Hydrolysis Eukaryota Fatty acid Biological Transport Transporter Flippase acyl-CoA Peroxisome 030104 developmental biology chemistry β-oxidation ATP-Binding Cassette Transporters ABC transporter Acyl Coenzyme A thioesterase Biochemical Society Focused Meetings Hydrophobic and Hydrophilic Interactions asymmetry |
| Zdroj: | Biochemical Society Transactions |
| ISSN: | 1470-8752 0300-5127 |
| Popis: | Import of β-oxidation substrates into peroxisomes is mediated by ATP binding cassette (ABC) transporters belonging to subfamily D. In order to enter the β-oxidation pathway, fatty acids are activated by conversion to fatty acyl-CoA esters, a reaction which is catalysed by acyl-CoA synthetases (ACSs). Here, we present evidence for an unusual transport mechanism, in which fatty acyl-CoA substrates are accepted by ABC subclass D protein (ABCD) transporters, cleaved by the transporters during transit across the lipid bilayer to release CoA, and ultimately re-esterified in the peroxisome lumen by ACSs which interact with the transporter. We propose that this solves the biophysical problem of moving an amphipathic molecule across the peroxisomal membrane, since the intrinsic thioesterase activity of the transporter permits separate membrane translocation pathways for the hydrophobic fatty acid moiety and the polar CoA moiety. The cleavage/re-esterification mechanism also has the potential to control entry of disparate substrates into the β-oxidation pathway when coupled with distinct peroxisomal ACSs. A different solution to the movement of amphipathic molecules across a lipid bilayer is deployed by the bacterial lipid-linked oligosaccharide (LLO) flippase, PglK, in which the hydrophilic head group and the hydrophobic polyprenyl tail of the substrate are proposed to have distinct translocation pathways but are not chemically separated during transport. We discuss a speculative alternating access model for ABCD proteins based on the mammalian ABC transporter associated with antigen processing (TAP) and compare it to the novel mechanism suggested by the recent PglK crystal structures and biochemical data. |
| Databáze: | OpenAIRE |
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