Hydrophobicity of the peptide CO···HN hydrogen-bonded group

Journal of Biological Chemistry

Ladokhin

Jayasinghe

et al. 2001

296

229

Constitutive ␣-helical membrane proteins (MPs) 1 are assembled in membranes by means of a translocation/insertion process that involves the translocon complex (1). After release into the membrane's bilayer fabric, a MP resides stably in a thermodynamic free energy minimum (evidence reviewed in Refs. 2 and 3). This means that the prediction of MP structure from the amino acid sequence is fundamentally a problem of physical chemistry, albeit a complex one. Physical influences that shape MP structure include interactions of the polypeptide chains with water, each other, the bilayer hydrocarbon core, the bilayer interfaces, and cofactors (Fig. 1). Two recent reviews (3, 4) provide extensive discussions of the evolution, structure, and thermodynamic stability of MPs. Here we provide a distilled (and updated) overview that addresses four broad questions.

Section: Coming To Thermodynamic Terms With Insolublementioning

confidence: 99%

How Membranes Shape Protein Structure

Journal of Biological Chemistry

Ladokhin

Jayasinghe

et al. 2001

296

229

“…These values will be countered by the cost of partitioning H-bonded peptide bonds (vG Hbond ). If Roseman's estimate [15] for vG Hbond of about 0.6 kcal/mol per H-bonded CONH holds for membranes, the favorable hydrophobic free energies of transfer would be reduced by V12 kcal/mol. The insertion of both the alanine and the leucine helices would be favored in that case.…”

Section: Introductionmentioning

confidence: 99%

“…The main source of this stability arises from the high cost of breaking H-bonds in non-polar environments. The cost of partitioning a peptide bond (CONH) into CCl 4 from water has been estimated by Roseman [15] to be V6 kcal/mol when not H-bonded, but only 0.6 kcal/mol when H-bonded. These values suggest a cost of V100 kcal/mol for unfolding a helix of 20 amino acids within a non-polar environment.…”

Section: Introductionmentioning

confidence: 99%

Hydrophobic interactions of peptides with membrane interfaces

Biochimica et Biophysica Acta (BBA) - Reviews on Biomembranes

Wimley

1998

514

462

The thermodynamic principles underlying the structural stability of membrane proteins are difficult to obtain directly from whole proteins because of intractable problems related to insolubility in the aqueous phase and extreme stability in the membrane phase. The principles must therefore be surmised from studies of the interactions of small peptides with lipid bilayers. This review is concerned with the hydrophobic interactions of such peptides with the interfacial regions of lipid bilayers. We first develop a general framework for thinking about the thermodynamics of membrane protein stability that centers on interfacial interactions and review the structural and chemical evidence that supports this interface-centered point of view. We then describe an experimentally determined whole-residue interfacial hydrophobicity scale that reveals the central role of the peptide bond in partitioning and folding. Finally, we consider the complexity and diversity of interfacial interactions revealed by differences between side-chain hydrophobicities determined using different classes of peptides. ß 1998 Elsevier Science B.V. All rights reserved.

“…The energetic cost of transferring a >CO or >NH group from water to a nonpolar region is 2-3 kcal/mol (Engelman & Steitz, 1981). An analysis by Roseman (1988) indicates an unbounded >NH and >CO pair requires about 6 kcal/mol to be buried in a nonpolar environment. Thus, the four pairs at the ends of a helical hairpin would require 24 kcal/mol to insert into the bilayer interior.…”

Section: Discussionmentioning

confidence: 99%

Observations concerning topology and locations of helix ends of membrane proteins of known structure

Jacobs²

1990

J. Membrain Biol.

Hydropathy plots of amino acid sequences reveal the approximate locations of the transbilayer helices of membrane proteins of known structure and are thus used to predict the helices of proteins of unknown structure. Because the three-dimensional structures of membrane proteins are difficult to obtain, it is important to be able to extract as much information as possible from hydropathy plots. We describe an "augmented" hydropathy plot analysis of the three membrane proteins of known structure, which should be useful for the systematic examination and comparison of membrane proteins of unknown structure. The sliding-window analysis utilizes the floating interfacial hydrophobicity scale [IFH(h)] of Jacobs and White (Jacobs, R.E., White, S. H., 1989. Biochemistry 28:3421-3437) and the reverse-turn (RT) frequencies of Levitt (Levitt, M., 1977, Biochemistry 17:4277-4285). The IFH(h) scale allows one to examine the consequences of different assumptions about the average hydrogen bond status (h = 0 to 1) of polar side chains. Hydrophobicity plots of the three proteins show that (i) the intracellular helix-connecting links and chain ends can be distinguished from the extracellular ones and (ii) the main peaks of hydrophobicity are bounded by minor ones which bracket the helix ends. RT frequency plots show that (iii) the centers of helices are usually very close to wide-window minima of average RT frequency and (iv) helices are always bounded by narrow-window maxima of average RT frequency. The analysis suggests that side-chain hydrogen bonding with membrane components during folding may play a key role in insertion.