Energetics, stability, and prediction of transmembrane helices

Sajith Jayasinghe, Kalina A Hristova, Stephen H. White

Research output: Contribution to journalArticle

Abstract

We show that the peptide backbone of an α-helix places a severe thermodynamic constraint on transmembrane (TM) stability. Neglect of this constraint by commonly used hydrophobicity scales underlies the notorious uncertainty of TM helix prediction by sliding-window hydropathy plots of membrane protein (MP) amino acid sequences. We find that an experiment-based whole-residue hydropathy scale (WW scale), which includes the backbone constraint, identifies TM helices of membrane proteins with an accuracy greater than 99%. Furthermore, it correctly predicts the minimum hydrophobicity required for stable single-helix TM insertion observed in Escherichia coli. In order to improve membrane protein topology prediction further, we introduce the augmented WW (aWW) scale, which accounts for the energetics of salt-bridge formation. An important issue for genomic analysis is the ability of the hydropathy plot method to distinguish membrane from soluble proteins. We find that the method falsely predicts 17 to 43% of a set of soluble proteins to be MPs, depending upon the hydropathy scale used.

Original languageEnglish (US)
Pages (from-to)927-934
Number of pages8
JournalJournal of Molecular Biology
Volume312
Issue number5
DOIs
StatePublished - Oct 5 2001
Externally publishedYes

Fingerprint

Membrane Proteins
Hydrophobic and Hydrophilic Interactions
Thermodynamics
Uncertainty
Amino Acid Sequence
Salts
Escherichia coli
Peptides
Proteins

Keywords

  • Genomic analysis
  • Hydropathy plots
  • Membrane proteins
  • Peptide bond
  • Structure prediction

ASJC Scopus subject areas

  • Virology

Cite this

Energetics, stability, and prediction of transmembrane helices. / Jayasinghe, Sajith; Hristova, Kalina A; White, Stephen H.

In: Journal of Molecular Biology, Vol. 312, No. 5, 05.10.2001, p. 927-934.

Research output: Contribution to journalArticle

Jayasinghe, Sajith ; Hristova, Kalina A ; White, Stephen H. / Energetics, stability, and prediction of transmembrane helices. In: Journal of Molecular Biology. 2001 ; Vol. 312, No. 5. pp. 927-934.
@article{fbadb600fbc946529c7e43de9d297e56,
title = "Energetics, stability, and prediction of transmembrane helices",
abstract = "We show that the peptide backbone of an α-helix places a severe thermodynamic constraint on transmembrane (TM) stability. Neglect of this constraint by commonly used hydrophobicity scales underlies the notorious uncertainty of TM helix prediction by sliding-window hydropathy plots of membrane protein (MP) amino acid sequences. We find that an experiment-based whole-residue hydropathy scale (WW scale), which includes the backbone constraint, identifies TM helices of membrane proteins with an accuracy greater than 99{\%}. Furthermore, it correctly predicts the minimum hydrophobicity required for stable single-helix TM insertion observed in Escherichia coli. In order to improve membrane protein topology prediction further, we introduce the augmented WW (aWW) scale, which accounts for the energetics of salt-bridge formation. An important issue for genomic analysis is the ability of the hydropathy plot method to distinguish membrane from soluble proteins. We find that the method falsely predicts 17 to 43{\%} of a set of soluble proteins to be MPs, depending upon the hydropathy scale used.",
keywords = "Genomic analysis, Hydropathy plots, Membrane proteins, Peptide bond, Structure prediction",
author = "Sajith Jayasinghe and Hristova, {Kalina A} and White, {Stephen H.}",
year = "2001",
month = "10",
day = "5",
doi = "10.1006/jmbi.2001.5008",
language = "English (US)",
volume = "312",
pages = "927--934",
journal = "Journal of Molecular Biology",
issn = "0022-2836",
publisher = "Academic Press Inc.",
number = "5",

}

TY - JOUR

T1 - Energetics, stability, and prediction of transmembrane helices

AU - Jayasinghe, Sajith

AU - Hristova, Kalina A

AU - White, Stephen H.

PY - 2001/10/5

Y1 - 2001/10/5

N2 - We show that the peptide backbone of an α-helix places a severe thermodynamic constraint on transmembrane (TM) stability. Neglect of this constraint by commonly used hydrophobicity scales underlies the notorious uncertainty of TM helix prediction by sliding-window hydropathy plots of membrane protein (MP) amino acid sequences. We find that an experiment-based whole-residue hydropathy scale (WW scale), which includes the backbone constraint, identifies TM helices of membrane proteins with an accuracy greater than 99%. Furthermore, it correctly predicts the minimum hydrophobicity required for stable single-helix TM insertion observed in Escherichia coli. In order to improve membrane protein topology prediction further, we introduce the augmented WW (aWW) scale, which accounts for the energetics of salt-bridge formation. An important issue for genomic analysis is the ability of the hydropathy plot method to distinguish membrane from soluble proteins. We find that the method falsely predicts 17 to 43% of a set of soluble proteins to be MPs, depending upon the hydropathy scale used.

AB - We show that the peptide backbone of an α-helix places a severe thermodynamic constraint on transmembrane (TM) stability. Neglect of this constraint by commonly used hydrophobicity scales underlies the notorious uncertainty of TM helix prediction by sliding-window hydropathy plots of membrane protein (MP) amino acid sequences. We find that an experiment-based whole-residue hydropathy scale (WW scale), which includes the backbone constraint, identifies TM helices of membrane proteins with an accuracy greater than 99%. Furthermore, it correctly predicts the minimum hydrophobicity required for stable single-helix TM insertion observed in Escherichia coli. In order to improve membrane protein topology prediction further, we introduce the augmented WW (aWW) scale, which accounts for the energetics of salt-bridge formation. An important issue for genomic analysis is the ability of the hydropathy plot method to distinguish membrane from soluble proteins. We find that the method falsely predicts 17 to 43% of a set of soluble proteins to be MPs, depending upon the hydropathy scale used.

KW - Genomic analysis

KW - Hydropathy plots

KW - Membrane proteins

KW - Peptide bond

KW - Structure prediction

UR - http://www.scopus.com/inward/record.url?scp=0035812599&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035812599&partnerID=8YFLogxK

U2 - 10.1006/jmbi.2001.5008

DO - 10.1006/jmbi.2001.5008

M3 - Article

C2 - 11580239

AN - SCOPUS:0035812599

VL - 312

SP - 927

EP - 934

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

SN - 0022-2836

IS - 5

ER -