The amphipathic helix in the exchangeable apolipoproteins: a review of secondary structure and function.
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.
Segrest
J P
JP
Department of Medicine, UAB Medical Center, Birmingham 35294.
Jones
M K
MK
De Loof
H
H
Brouillette
C G
CG
Venkatachalapathi
Y V
YV
Anantharamaiah
G M
GM
D000595:Amino Acid Sequence; D000818:Animals; D001053:Apolipoproteins / Q000737:chemistry*; D006801:Humans; D008969:Molecular Sequence Data; D011487:Protein Conformation
D001053:Apolipoproteins