title: Adaptations of protein structure and function to temperature: there is more than one way to 'skin a cat'.
abstract: Sensitivity to temperature helps determine the success of organisms in all habitats, and is caused by the susceptibility of biochemical processes, including enzyme function, to temperature change. A series of studies using two structurally and catalytically related enzymes, A4-lactate dehydrogenase (A4-LDH) and cytosolic malate dehydrogenase (cMDH) have been especially valuable in determining the functional attributes of enzymes most sensitive to temperature, and identifying amino acid substitutions that lead to changes in those attributes. The results of these efforts indicate that ligand binding affinity and catalytic rate are key targets during temperature adaptation: ligand affinity decreases during cold adaptation to allow more rapid catalysis. Structural changes causing these functional shifts often comprise only a single amino acid substitution in an enzyme subunit containing approximately 330 residues; they occur on the surface of the protein in or near regions of the enzyme that move during catalysis, but not in the active site; and they decrease stability in cold-adapted orthologs by altering intra-molecular hydrogen bonding patterns or interactions with the solvent. Despite these structure-function insights, we currently are unable to predict a priori how a particular substitution alters enzyme function in relation to temperature. A predictive ability of this nature might allow a proteome-wide survey of adaptation to temperature and reveal what fraction of the proteome may need to adapt to temperature changes of the order predicted by global warming models. Approaches employing algorithms that calculate changes in protein stability in response to a mutation have the potential to help predict temperature adaptation in enzymes; however, using examples of temperature-adaptive mutations in A4-LDH and cMDH, we find that the algorithms we tested currently lack the sensitivity to detect the small changes in flexibility that are central to enzyme adaptation to temperature.
authors.affiliation: Biology Department, Franklin & Marshall College, Lancaster, PA 17603, USA peter.fields@fandm.edu.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Fields
authors.affiliation: State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen 361005, China.
authors.forename: Yunwei
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China.
authors.forename: Xianliang
authors.initials: X
authors.lastname: Meng
authors.affiliation: Hopkins Marine Station, Department of Biology, Stanford University, Pacific Grove, CA 93940, USA.
authors.forename: George N
authors.initials: GN
authors.lastname: Somero
mesh_terms: D000222:Adaptation, Physiological; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D007770:L-Lactate Dehydrogenase / Q000737:chemistry* / Q000502:physiology; D008291:Malate Dehydrogenase / Q000737:chemistry* / Q000502:physiology; D008969:Molecular Sequence Data; D011487:Protein Conformation; D013696:Temperature
chemical_list: D007770:L-Lactate Dehydrogenase; D008291:Malate Dehydrogenase
keywords: A4-lactate dehydrogenase; Cytosolic malate dehydrogenase; Protein stability; Temperature adaptation