Transmembrane passage of hydrophobic compounds through a protein channel wall.
Transmembrane passage of hydrophobic compounds through a protein channel wall.
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DOI：
10.1038/nature07678
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发表时间：
2009-03-19
期刊：
影响因子：
64.8
通讯作者：
van den Berg, Bert
中科院分区：
文献类型：
--
作者：
Hearn, Elizabeth M.;Patel, Dimki R.;Lepore, Bryan W.;Indic, Mridhu;van den Berg, Bert
Membrane proteins that transport hydrophobic compounds play important roles in multi-drug resistance and can cause a number of diseases, underscoring the importance of protein-mediated transport of hydrophobic compounds. Hydrophobic compounds readily partition into regular membrane lipid bilayers, and their transport through an aqueous protein channel is energetically unfavourable. Alternative transport models, involving acquisition from the lipid bilayer by lateral diffusion have been proposed for hydrophobic substrates. To date, all transport proteins for which a lateral diffusion mechanism has been proposed function as efflux pumps. Here we present the first example of a lateral diffusion mechanism for the uptake of hydrophobic substrates, by the Escherichia coli outer membrane long-chain fatty acid (LCFA) transporter FadL. A FadL mutant in which a lateral opening in the barrel wall is constricted, but which is otherwise structurally identical to wild-type FadL, does not transport substrates. A crystal structure of FadL from Pseudomonas aeruginosa shows that the opening in the wall of the β-barrel is conserved and delineates a long, hydrophobic tunnel that could mediate substrate passage from the extracellular environment, through the polar lipopolysaccharide layer and, via the lateral opening in the barrel wall, into the lipid bilayer from where the substrate can diffuse into the periplasm. Since FadL homologues are found in pathogenic and biodegrading bacteria, our results have implications for combating bacterial infections and bioremediating xenobiotics in the environment.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
4.8
作者：
Hong, HD;Patel, DR;van den Berg, B
通讯作者：
van den Berg, B
DOI：
10.1107/s0907444998003254
发表时间：
1998-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Brunger, AT;Adams, PD;Warren, GL
通讯作者：
Warren, GL
影响因子：
13.8
作者：
HIGGINS, CF;GOTTESMAN, MM
通讯作者：
GOTTESMAN, MM
影响因子：
3.2
作者：
GUZMAN, LM;BELIN, D;BECKWITH, J
通讯作者：
BECKWITH, J