Protein Assembly and Metabolic Regulation: Physiological and Evolutionary Perspectives

Citations Over TimeTop 14% of 1990 papers

Abstract

Many physiologically important adjustments of metabolic activities are achieved by modifying the assembly states of proteins. These assembly-state changes involve the reversible aggregation of the subunits of multi-subunit proteins and the reversible binding of enzymes to other enzymes or to structural components of cells (compartmentation). Adaptive shifts in protein assembly states are key elements in both rapid metabolic adjustments, such as those occurring in transitions from slow to rapid muscular activity, and longer-term metabolic changes, such as those associated with different types of dormancy. Changes in subunit assembly state allow sharp "on-off" regulation of enzymes, as manifested in the regulation of phosphofructokinase (PFK) and trehalase activities by transitions in pH. Changes in the aggregation states of multiprotein complexes alter the proximity of the several enzymes composing apathway, thereby altering the eiciency of metabolite transfer among enzymes of the sequence. Aggregation also may facilitate interaction between enzymes that generate a metabolite, for example, ATP, with other enzymes using this metabolite. The binding of glycolytic enzymes to the myofibrillar apparatus is a case in point. The enhancement of metabolic regulatory mechanisms made possible by these reversible changes in protein assembly is likely the selective advantage fostering the evolution of multiple protein-binding domains in many eukaryotic enzymes. A deeper understanding of multiprotein complexes, then, will not only advance knowledge of metabolic regulation, but in addition will help explain the evolutionary development oflarge, complex, and often highly conserved protein structures From an experimental standpoint, the differences in catalytic performance observed between a purified enzyme studied in a simple reaction mixture versus the same enzyme analyzed in a milieu that includes the otherproteins with which it interacts, and the modulators that regulate these protein-protein interactions, can be dramatic. This observation highlights the need for conducting enzymatic studies under conditions that simulate as closely aspossible the intracellular state.

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