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

Abstract

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.

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