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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 transmem brane 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.

Two fundamental question in our investigations of lipoprotein structure and function have been how do lipoproteins form, and what factors contribute to lipoprotein stability. In the simplest sense, apolipoproteins might be considered as polymeric detergents: within lipoproteins, the apolipoproteins, phospholipids, and cholesterol form a surface monolayer, which separates a core of neutral lipids from an external aqueous compartment. In the crudest verification of lipid-protein association, one finds that most of the plasma apolipoproteins spontaneously associate with highly turbid multibi-layers of phospholipid to form small lipid-protein complexes that are optically clear. In all such reassembly studies it has been found that phospholipids alone or with neutral lipids form complexes, but that the neutral lipids do not associate with apolipoproteins in the absence of phospholipids. Therefore, the phospholipid-apolipoprotein interaction would appear to be a key structural unit in the organization of a lipoprotein. It is the structure and dynamics of this association which we will attempt to correlate with what is known about the structure of lipoproteins, lipids and apoproteins.

Plasma lipoproteins play a central role in the regulation of lipid metabolism. Details of the organization of plasma lipoproteins at the molecular level are necessary for a basic understanding of the principles that govern lipoprotein assembly, interconversion, and metabolism.

Since the isolation and sequencing of the apolipoproteins, several attempts have been made towards the identification of the structural domains accounting for the specific properties of these proteins (1). Apolipoproteins are responsible for the transport of apolar lipid molecules in plasma. Their 1ipid-binding properties have been attributed to the amphipathic helices which are present in all of the apolipoproteins (2). The sequences of these proteins have a high degree of internal homology and the various apolipoproteins, including apo B share homologous domains with each other (3).

The value of a model is that is simplifies the description of a system: it focuses attention onto potentially critical features, and it will be superseded by better models that explain more. Above all it suggests critical and focused experimental tests designed to refine the model, eliminate inconsistency, and uncover function.