LDL receptor-binding domain of Apolipoprotein E3
Homo sapiens (human)
Lipids, by definition, are rather hydrophobic molecules and do not mix well with water. They are, however, important constituents of cells, and their transport inside the body, in the blood, is accomplished by enclosing them in particles. One example of such a transport vehicle are the low-density lipoprotein (LDL) particles. They are formed by a single layer membrane of phospholipids, pointing their hydrophilic heads to the outside and their hydrophobic hydrocarbon chains inside. Such constructs are also called miscelles. At the surface of the LDL particle sits a protein called apolipoprotein. There are two different types of this protein, apolipoprotein E (apoE) and apolipoprotein B. These apolipoproteins bind to cell surface transmembrane proteins called LDL receptors. ApoE is a relatively small protein with about 300 residues. This protein consists of two domains. These two domains are related to different functions. The first domain, comprising roughly the first two thirds of the polypeptide chain, will attach the LDL receptor. Naturally occurring mutations in this domain can result in atherosclerosis. It is therefore of interest to understand its structure as a contribution to understanding the causes of the disease. The structure of the core of the LDL-binding domain of apoE is extremely simple.
It is shown here with roughly a hundred residue missing on either side. It takes the form of a common structural motif found in other proteins, the four-helix bundle. Four helices align in parallel to form a rather rigid cylinder-shaped molecule roughly 65 angstrom long and about 20 angstrom in diameter. The amino acids responsible for the binding of apoE to the LDL receptors are located close together on one long helix.
Protein Data Bank (PDB)
Wilson, C. Wardell, M.R. Weisgraber, K.H. Mahley, R.W. Agard, D.A.; "Three-dimensional structure of the LDL receptor-binding domain of human apolipoprotein E."; Science; (1991) 252:1817-1822 PubMed:2063194.
author: Arno Paehler