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Self-association of transmembrane alpha-helices in model membranes - Importance of helix orientation and role of hydrophobic mismatch

Sparr, Emma LU ; Ash, W L; Rijkers, D T S; Hemminga, M A; Tieleman, D P and Killian, J A (2005) In Journal of Biological Chemistry 280(47). p.39324-39331
Abstract
Interactions between transmembrane helices play a key role in almost all cellular processes involving membrane proteins. We have investigated helix-helix interactions in lipid bilayers with synthetic tryptophan-flanked peptides that mimic the membrane spanning parts of membrane proteins. The peptides were functionalized with pyrene to allow the self-association of the helices to be monitored by pyrene fluorescence and Trp-pyrene fluorescence resonance energy transfer (FRET). Specific labeling of peptides at either their N or C terminus has shown that helix-helix association occurs almost exclusively between antiparallel helices. Furthermore, computer modeling suggested that antiparallel association arises primarily from the electrostatic... (More)
Interactions between transmembrane helices play a key role in almost all cellular processes involving membrane proteins. We have investigated helix-helix interactions in lipid bilayers with synthetic tryptophan-flanked peptides that mimic the membrane spanning parts of membrane proteins. The peptides were functionalized with pyrene to allow the self-association of the helices to be monitored by pyrene fluorescence and Trp-pyrene fluorescence resonance energy transfer (FRET). Specific labeling of peptides at either their N or C terminus has shown that helix-helix association occurs almost exclusively between antiparallel helices. Furthermore, computer modeling suggested that antiparallel association arises primarily from the electrostatic interactions between alpha-helix backbone atoms. We propose that such interactions may provide a force for the preferentially antiparallel association of helices in polytopic membrane proteins. Helix-helix association was also found to depend on the lipid environment. In bilayers of dioleoylphosphatidylcholine, in which the hydrophobic length of the peptides approximately matched the bilayer thickness, association between the helices was found to require peptide/lipid ratios exceeding 1/25. Self-association of the helices was promoted by either increasing or decreasing the bilayer thickness, and by adding cholesterol. These results indicate that helix-helix association in membrane proteins can be promoted by unfavorable protein-lipid interactions. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
280
issue
47
pages
39324 - 39331
publisher
ASBMB
external identifiers
  • wos:000233362200052
  • scopus:28244458040
ISSN
1083-351X
DOI
10.1074/jbc.M502810200
language
English
LU publication?
yes
id
59e3068b-b70c-4250-8c85-cd83ea6b0b77 (old id 157611)
date added to LUP
2007-07-12 11:47:45
date last changed
2017-07-09 03:37:43
@article{59e3068b-b70c-4250-8c85-cd83ea6b0b77,
  abstract     = {Interactions between transmembrane helices play a key role in almost all cellular processes involving membrane proteins. We have investigated helix-helix interactions in lipid bilayers with synthetic tryptophan-flanked peptides that mimic the membrane spanning parts of membrane proteins. The peptides were functionalized with pyrene to allow the self-association of the helices to be monitored by pyrene fluorescence and Trp-pyrene fluorescence resonance energy transfer (FRET). Specific labeling of peptides at either their N or C terminus has shown that helix-helix association occurs almost exclusively between antiparallel helices. Furthermore, computer modeling suggested that antiparallel association arises primarily from the electrostatic interactions between alpha-helix backbone atoms. We propose that such interactions may provide a force for the preferentially antiparallel association of helices in polytopic membrane proteins. Helix-helix association was also found to depend on the lipid environment. In bilayers of dioleoylphosphatidylcholine, in which the hydrophobic length of the peptides approximately matched the bilayer thickness, association between the helices was found to require peptide/lipid ratios exceeding 1/25. Self-association of the helices was promoted by either increasing or decreasing the bilayer thickness, and by adding cholesterol. These results indicate that helix-helix association in membrane proteins can be promoted by unfavorable protein-lipid interactions.},
  author       = {Sparr, Emma and Ash, W L and Rijkers, D T S and Hemminga, M A and Tieleman, D P and Killian, J A},
  issn         = {1083-351X},
  language     = {eng},
  number       = {47},
  pages        = {39324--39331},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Self-association of transmembrane alpha-helices in model membranes - Importance of helix orientation and role of hydrophobic mismatch},
  url          = {http://dx.doi.org/10.1074/jbc.M502810200},
  volume       = {280},
  year         = {2005},
}