Meeting Abstract

69.1  Saturday, Jan. 5  Lessons from cold-adapted enzymes: Can protein adaptation to temperature be simple and quick? SOMERO, GEORGE; Stanford University somero@stanford.edu

Fascination with how proteins manage to work well at near-freezing temperatures has led to detailed study of enzymatic and structural proteins of Antarctic notothenioid fishes. Discovery that lactate dehydrogenase (LDH) orthologs of notothenioids have extremely high intrinsic rates of activity (kcat values) and appropriate substrate binding affinities (Km) for function in the cold has prompted investigation of the underlying changes in amino acid sequence that generate these adaptations. One key finding of these comparative studies is that adaptation to cold can be achieved by only one or two amino acid substitutions and need not involve a wholesale redesign of protein structure. This discovery has prompted wide-ranging studies of other proteins and other taxa, to see if such a ‘simple’ solution to temperature adaptation is prevalent. Indeed, studies of orthologous malate dehydrogenases (cMDHs) of several invertebrate lineages have shown that (i) a single amino acid substitution can suffice to achieve adaptation, (ii) a number of sites in the sequence are candidates for adaptive change, and (iii) the primary effect of these amino acid substitutions is to modify the conformational mobility of regions of the enzyme that move during function. Active (catalytic) sites themselves are fully conserved. Importantly, studies of different proteins suggest that not all proteins are as thermally sensitive as LDH and cMDH. Thus, temperature adaptation may not involve modification of the entire proteome. These findings have implications for rates of protein evolution, notably in the context of a rapidly warming planet.