The formation of closed structures, such as rings, tubes, or spheres, provides additional stability because it increases the number of bonds between the protein subunits. Moreover, because such a structure is created by mutually dependent, cooperative interactions between subunits, a relatively small change that affects each subunit individually can cause the structure to assemble or disassemble. These principles are dramatically illustrated in the protein coat or capsid of many simple viruses, which takes the form of a hollow sphere based on an icosahedron (Figure 3–27). Capsids are often made of hundreds of identical protein subunits that enclose and protect the viral nucleic acid (Figure 3–28). The protein in such a capsid must have a particularly adaptable structure: not only must it make several different kinds of contacts to create the sphere, it must also change this arrangement to let the nucleic acid out to initiate viral replication once the virus has entered a cell.
Many Structures in Cells Are Capable of Self-Assembly
The information for forming many of the complex assemblies of macromolecules in cells must be contained in the subunits themselves, because purified subunits can spontaneously assemble into the final structure under the appropriate conditions. The first large macromolecular aggregate shown to be capable of self-assembly from its component parts was tobacco mosaic virus (TMV ). This virus is a long rod in which a cylinder of protein is arranged around a helical RNA core (Figure 3–29). If the dissociated RNA and protein subunits are mixed together in solution, they recombine to form fully active viral particles. The assembly process is unexpectedly complex and includes the formation of double rings of protein, which serve as intermediates that add to the growing viral coat.
Another complex macromolecular aggregate that can reassemble from its component parts is the bacterial ribosome. This structure is composed of about 55 different protein molecules and 3 different rRNA molecules. Incubating a mixture of the individual components under appropriate conditions in a test tube causes them to spontaneously re-form the original structure. Most importantly, such reconstituted ribosomes are able to catalyze protein synthesis. As might be expected, the reassembly of ribosomes follows a specific pathway: after certain proteins have bound to the RNA, this complex is then recognized by other proteins, and so on, until the structure is complete.
It is still not clear how some of the more elaborate self-assembly processes are regulated. Many structures in the cell, for example, seem to have a precisely defined length that is many times greater than that of their component macromolecules. How such length determination is achieved is in many cases a mystery. In
Figure 3–26 Single protein subunits form protein assemblies that feature multiple protein–protein contacts. Hexagonally packed globular protein subunits are shown here forming either flat sheets or tubes. Generally, such large structures are not considered to be single “molecules.” Instead, like the actin filament described previously, they are viewed as assemblies formed of many different molecules.
Figure 3–27 The protein capsid of a virus. The structure of the simian virus SV40 capsid has been determined by x-ray crystallography and, as for the capsids of many other viruses, it is known in atomic detail. (Courtesy of Robert Grant, Stephan Crainic, and James M. Hogle.) capsid protein intact virus monomer particle shown as (90 dimers) the simplest case, a long core protein or other macromolecule provides a scaffold that determines the extent of the final assembly. This is the mechanism that determines the length of the TMV particle, where the RNA chain provides the core. Similarly, a core protein interacting with actin is thought to determine the length of the thin filaments in muscle.