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The Nature of the Hydrophobic Binding of Small Peptides at the Bilayer Interface: Implications for the Insertion of Transbilayer Helices

Jacobs, Russell E. and White, Stephen H. (1989) The Nature of the Hydrophobic Binding of Small Peptides at the Bilayer Interface: Implications for the Insertion of Transbilayer Helices. Biochemistry, 28 (8). pp. 3421-3437. ISSN 0006-2960. doi:10.1021/bi00434a042.

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One method of obtaining useful information about the physical chemistry of peptide/bilayer interactions is to relate thermodynamic parameters of the interactions to structural parameters obtained by diffraction methods. We report here the results of the application of this approach to interactions of hydrophobic tripeptides of the form Ala-X-Ala-0-tert-butyl with lipid bilayers. The thermodynamic constants (ΔG_t> ΔH_1, and Δ1) for the transfer of the tripeptides from water into DMPC vesicles were determined for X = Leu, Phe, and Trp and found to be consistent with those expected for hydrophobic interactions above the phase transition of DMPC. Combining these results with the earlier ones of Jacobs and White [(1986) Biochemistry 25, 2605-2612], the favorable free energies of transfer with different amino acids in the -X- position increase in the order Gly <Ala <Leu < Phe < Trp in agreement with the Nozaki and Tanford [(1971) J. Biol. Chem. 246, 2211-2217) hydrophobicity scale. Determination of the location of Ala-[2H5]Trp-Ala-O-tert-butyl in oriented DOPC bilayers by neutron diffraction shows that the most hydrophobic peptide of the series is confined to the bilayer headgroup/water region. Refinement of the diffraction measurements shows that only 13% of the tryptophan is associated with the hydrocarbon core. The distribution of the water tends to mirror that of the peptide. Unlike peptide-free bilayers, 5% of the water penetrates the hydrocarbon, which is about 100-fold greater than expected. A quantitative thermodynamic analysis of the interfacial binding of the peptides suggests that (1) the hydrophobic interactions are 60-70% complete upon binding at the bilayer interface, (2) the interface is likely to play an important role in helix formation and insertion, (3) the hydrogen bond status of amino acid side chains is crucial to insertion, and ( 4) an a priori lack of knowledge of the status of such bonds could limit the precision of hydrophobicity plots. We introduce an interfacial hydrophobicity scale, IFH(h), with a variable hydrogen bond parameter (h) that permits one to consider explicitly hydrogen bonding in transbilayer helix searches.

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Jacobs, Russell E.0000-0002-1382-8486
Additional Information:© 1989 American Chemical Society. Received January 27, 1988; Revised Manuscript Received December 7, 1988. This work was supported by a grant from the National Science Foundation (DMB-8412754) and the American Heart Association California Affiliate with funds contributed by the Orange County, CA, Chapter. R.E.J. is an Established Investigator of the American Heart Association. Parts of the research were carried out at Brookhaven National Laboratory, Upton, Long Island, NY, under the auspices of the U.S. Department of Energy with the additional support of the National Science Foundation. We are pleased to acknowledge the excellent technical assistance of April Diaz and many stimulating discussions with Dr. Glen King in the early phases of the diffraction work. We thank Dr. Michael Wiener for his comments on the manuscript.
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American Heart Association, California AffiliateUNSPECIFIED
Department of Energy (DOE)UNSPECIFIED
Issue or Number:8
Record Number:CaltechAUTHORS:20160516-132217860
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Official Citation:The nature of the hydrophobic binding of small peptides at the bilayer interface: implications for the insertion of transbilayer helices Russell E. Jacobs and Stephen H. White Biochemistry 1989 28 (8), 3421-3437 DOI: 10.1021/bi00434a042
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:67132
Deposited By: Ruth Sustaita
Deposited On:16 May 2016 21:10
Last Modified:11 Nov 2021 00:27

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