Structural theme, membrane proteins

At present there is considerable interest in the way in which the con-stituents of membranes are associated to form the dynamic complex entity of the cell membrane. Speculations range from the Danielli-type structure, first advanced in 1935, to structures which now place greater emphasis on the so-called hydrophobic bonding of the lipid polymethylene chains and amino acids of the membrane protein (10). Various other speculations about the associations of the membrane components are built around these two main themes. In a field of research where there are such a considerable speculation and divergence of opinion, this usually indicates a shortage of experimental information rather than variations in perspicacity. This seems to be true of our present knowledge of membrane structure. 

At first it might seem contradictory that the addition of another macro-molecular component, namely, the lipid bilayer, could simplify understanding of the protein mechanism. Indeed, many membrane proteins have substantial mass that protrudes into the aqueous space and that is likely to be as complex in operation as soluble proteins. However, many integral membrane proteins share a common structural theme, namely, a core of almost parallel, bilayer-spanning helices or sheets. The structural order of these helices is a direct consequence of the amphiphilic environment introduced by the lipid bilayer. The discussion that follows will focus on mechanistic forces as they apply to this common core, and not to large aqueous protrusions. By contrast, aque-ously soluble proteins are structurally more diverse and, in the absence of a common structural theme, cannot be approached in the same manner. 

A similar approach is used to form various large structures in which the repeating components associate by non-covalent interactions. For instance, the fibers of the cytoskeleton are composed of many repeating protein molecules. And, as we discuss below, phospholipids assemble noncovalently to form a two-layered (bilayer) structure that is the basis of all cellular membranes (see Figure 2-11). Thus a repeating theme in biology is the construction of large molecules and structures by the covalent or noncovalent association of many similar or identical smaller molecules. 

The most prominent feature of cytocidal virus-cell interaction is the inhibition of host macromolecular synthesis. The understanding of the molecular basis of this inhibition where the host DNA, RNA, and protein synthesis is selectively blocked while virus replication goes on is the central theme of this chapter. The mechanisms by which particular virus-cell combinations accomplish this inhibition appear to be quite variable, and a number of hypotheses have been proposed to explain this phenomenon. It has been suggested that inhibition of host macromolecular synthesis by cytocidal viruses may be initiated by (1) structural components of the input virion, (2) virus-induced products synthesized in the course of infection, (3) viral nucleic acids as either replicative intermediates (double-stranded RNA) or as multiple copies of the viral genome (single-stranded RNA), or (4) the results of perturbations of the cellular membrane which allow for changes in the normal ion concentrations within the cell. 

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