Role of amphipathic helixes in HDL structure/function.
In a recent analysis we classified amphipathic helix domains into a minimum of seven distinct classes. Four amphipathic helix classes are found in lipid-associating proteins: apolipoproteins, certain polypeptide hormones, polypeptide venoms and antibiotics, and certain complex transmembrane proteins. Three amphipathic helix classes are involved in both intra- and intermolecular protein-protein interactions: calmodulin-regulated protein kinases, coiled-coil containing proteins that include the so-called leucine zipper, and globular helical proteins. Three central hypothesis have been developed in our studies of the apolipoprotein class of amphipathic helixes: 1) The "Snorkel" hypothesis proposes that when the amphipathic helix is associated with phospholipid, amphipathic basic residues extend toward the polar face of the helix to insert their charged residues into the aqueous milieu: thus the entirety of the uncharged van der Waals' surface of the amphipathic helix is buried within the lipid. 2) We have formulated a hypothesis that Glutamyl residues located at positions 78 and 111 in apolipoprotein A-I on the nonpolar face of two amphipathic helical domains are critical to LCAT activation. 3) The hinged-domain hypothesis was proposed to explain the structural basis for the quantization of HDL subspecies, protein-protein interactions in HDL, and the HDL disc to sphere transformation.
Anantharamaiah
G M
GM
Department of Medicine, UAB Medical Center, Birmingham, Alabama 35294.
Brouillette
C G
CG
Engler
J A
JA
De Loof
H
H
Venkatachalapathi
Y V
YV
Boogaerts
J
J
Segrest
J P
JP
D000595:Amino Acid Sequence; D016632:Apolipoprotein A-I; D001054:Apolipoproteins A / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry*; D008969:Molecular Sequence Data; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D008075:Lipoproteins, HDL; D007862:Phosphatidylcholine-Sterol O-Acyltransferase