Subunit Assembly of Oligomeric Enzymes

Organic Material Department, Government Industrial Research Institute, Ikeda, Osaka 563, Japan 

The term quaternary structure was proposed to supplement the terms primary, secondary, and tertiary structure, 9 and refers to the spatial arrangement of noncovalently linked polypeptides which we shall call subunits. Generally, a subunit is defined as a tertiary structural unit composed of a single polypeptide, but the definition is somewhat ambiguous. In aspartate transcarbamoylase from Escherichia coli, for example, tertiary structural units composed of three catalytic polypeptide chains are called catalytic subunits and those composed of two regulatory chains are called regulatory subunits.2) 

In this review, we shall focus on new approaches with particular emphasis on the subunit assembly in the cell after a brief summary of the functional aspects of quaternary structure, because the comprehensive review of the quaternary structure written by Klotz, Darnall and Langerman3) in 1975 is essentially valid. 

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Monomeric intermediates during the assembly of oligomeric proteins are usually inactive and the formation of native quaternary structures are often a prerequisite for catalytic activity. One clear reason for this is that the active sites of some enzymes are located at the interface between subunits and are formed by amino acid residues from different subunits. Such examples are aspartate transcarbamoylase from K coli5) and ribulose bisphosphate carboxylase/oxygenase from Rhodospirillum rubrum.6)... 

Many other oligomeric enzymes and other complex assemblies of more than one kind of protein subunit are known. For example, the 2-oxoacid dehydrogenases are huge 2000- to 4000-kDa complexes containing three different proteins with different enzymatic activities in a cubic array (Fig. 15-14). The filaments of striated muscle (Chapter 19), antibodies and complement of blood (Chapter 31), and the tailed bacteriophages (Box 7-C ) all have complex molecular architectures. 

A large number of enzymes exist as symmetric macro-molecular assemblies where they commonly exhibit C and D point group symmetries and contain two-, three-, four-, and six-fold axes of symmetry. In the simplest cases this feature provides additional thermodynamic stability for a protein that would otherwise be rather small. In more complex arrangements the protein-protein interfaces form the active site such that the oligomerization is required for function. Finally, in the most highly evolved enzymes there is communication between the active sites that reside on symmetrically related subunits. This provides the foundation for enzyme regulation as observed in most allosteric enzymes. 

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