The amphipathic helix in the exchangeable apolipoproteins: a review of secondary structure and function.

Jp Segrest,Mk Jones,H De Loof,Cg Brouillette,Yv Venkatachalapathi,Gm Anantharamaiah

doi:10.1016/s0022-2275(20)41536-6

Abstract

Site-directed mutagenesis and other molecular biology-based techniques are now available for probing the amphipathic alpha helix structural motif in the exchangeable apolipoproteins. Here we survey the published literature on lipid-binding and functional domains in apolipoproteins A-I, A-II, A-IV, C-I, C-II, C-III, and E and compare these results with recently developed computer methods for analysis of the location and properties of amphipathic helixes. This comparison suggests that there are at least three distinct classes of amphipathic helixes (classes A, Y, and G*) in the exchangeable apolipoproteins whose distribution varies within and between the seven apolipoproteins. This comparison further suggests that lipid affinity resides largely in class A amphipathic helixes (Segrest, J. P., et al. 1990. Proteins. 8: 103) and that variations in structure and/or numbers of class A domains in individual apolipoproteins allow a range of lipid affinities from high to low. The positions of the four alpha helixes recently shown to form a 4-helix bundle globular structure in apoE (Wilson, C., et al. 1991. Science. 252: 1817) correspond closely to the four amino-terminal class G* amphipathic helixes of apoE identified by our computer analysis. It is of particular interest, therefore, that all of the exchangeable apolipoproteins except apoA-II and C-I, contain amphipathic helixes of class G*. Additional implications of amphipathic helix heterogeneity for the structure and function of the exchangeable apolipoproteins will be discussed.

Highlights

Sitedirected mutagenesis and other molecular biology-based techniques are available for probing the amphipathic a helix structural motif in the exchangeable apolipoproteins
By extrapolation from the membrane protein argument, and because a lipid-water interface can leave its signature in the form of an amphipathic helix, we suggest that algorithms for locating amphipathic helical domains in apolipoproteins can more reliably define the ends of lipid-associating amphipathic helical domains than it can define the ends of protein-associating domains
In the remainder of this section we briefly describe the algorithms used to localize the amphipathic helical domains in the exchangeable apolipoproteins A-I, A-11, A-IV, C-I

Summary

Introduction

Sitedirected mutagenesis and other molecular biology-based techniques are available for probing the amphipathic a helix structural motif in the exchangeable apolipoproteins. Studies of intact and fragmented apolipoproteins and model peptides, described earlier, support the idea that amphipathic helixes serve in general as the lipid-associating protein detergent domains for the exchangeable apolipoproteins.

Results

Conclusion