Principles of Protein Structure Determination - H. Schiltz 1982

Protein–ligand interactions
Protein interactions with other macromolecules
Lipoproteins

Proteins can specifically interact with other macromolecules, such as Nucleic Acids and Polysaccharides. Lipids are also classified among macromolecules because they form large aggregates In aqueous solutions. In Nucleoproteins, Glycoproteins, or Lipoproteins, protein may account for less than 50%, and the overall properties of these complexes are often determined by their non-protein moieties. Moreover, both the formation and structural stability of proteins can depend on their complex partners. This is most evident in Membrane Proteins that bridge different hydrocarbon segments of Cell/29.html">The Lipid Bilayer.

Proteins penetrate the interface between aqueous and nonpolar phases. Two vital biological Functions are rooted in protein-lipid interactions: The transport of lipids in aqueous solutions and membrane activity. The capacity of Blood Plasma to transport poorly soluble lipids—such as Cholesterol (2 mg is soluble in 1 l of a 150 mM NaCl solution, pH 7.4) or triacylglycerols—is enhanced 1,000-fold through The formation of specific lipoproteins. Such lipid-transporting proteins may play a role in atherosclerosis and other diseases, which explains the extensive literature dedicated to them [145, 694]. Considerable interest is also focused on the secondary and tertiary structures of lipoproteins. Attempts have been made to predict their structures based on the correlation (Chap. 6) between Secondary Structure and the Amino Acid Sequence of conventional Globular proteins [694]. Because crystallizing lipoproteins is rather difficult, more precise structural data are unlikely to become available in the near future.

In membranes, lipids form biological barriers and matrices, whereas specific Membrane Functions—such as transport, signal Transduction, and energy conversion—are carried out by proteins [19, 695–697]. Information regarding the Amino acid sequences within the intramembranous regions of proteins is extremely limited; however, it is known that these regions contain fairly extended stretches of nonpolar residues [698]. The most detailed information on tertiary structure has been obtained for a membrane protein from Halobacterium halobium [699, 700]. The subunit of this protein consists primarily of seven parallel or antiparallel a-helices spanning from one membrane surface to the other. Another well-studied system is discussed below.

The calcium pump is a classic, well-investigated membrane protein. The sarcoplasmic reticulum from Muscle tissue [701, 702] is a tubular system with a highly specialized membrane whose sole function is the release and sequestration of Calcium Ions [703, 704]. This is reflected by the fact that a single protein with a Molecular Weight of 100,000—known as the Ca²⁺-transporting ATPase or Ca²⁺ pump—constitutes more than 50% of the membrane mass and 80% of its total protein content. This protein forms a cylinder 50 Å in diameter and 80 Å in length, traversing the entire membrane layer, which is 60 to 90 Å thick. The membrane contains 90 (phospho)lipid molecules per Ca²⁺ pump molecule.

Clearly, the membrane and the Ca²⁺ pump form a functional unit, in which the membrane acts as a barrier preventing the return of accumulated calcium. Furthermore, the membrane serves as a two-dimensional solvent for the protein: as demonstrated in lipid-binding experiments with the purified protein, The surface of the Ca²⁺-transporting ATPase exhibits a higher affinity for a nonpolar environment than for Water. Because there is only one type of water but many types of lipid molecules, this broad spectrum of lipid species provides A wide variety of specific interactions with membrane proteins. The Role of individual lipid classes in a given membrane process is elucidated through model experiments [705, 705]. In the case of the calcium pump, a functionally active membrane system can be reconstituted by simply adding Phospholipids to the purified protein [701, 702].

Proteins move within the plane of the membrane. A bulky antibody attached to the extracellular domain of the Ca²⁺-transporting ATPase does not impede the translocation of calcium ions, indicating that Ca²⁺ translocation does not require the protein to rotate around an axis parallel to the membrane surface [707]. This appears to be a general rule for membrane proteins. On the other hand, proteins are capable of rotation [708] and lateral diffusion within the membrane plane; the actual degree of mobility depends on the PHYSICOCHEMICAL PROPERTIES OF the membrane and the guiding influence of protein contacts with both membrane surfaces. Lateral diffusion is essential for interactions among the components of a multicomponent, membrane-associated system, since functionally coupled membrane proteins are not always in direct physical contact with one another [709, 710].

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