Temperature and macromolecular structure and function.

Stability is frequently a knife-edge phenomenon and it is this aspect which is both essential for the effective involvement of macromolecules in the living cell and also provides the basis for the sensitivity of some macromolecular systems to temperature. The response of proteins and nucleic acids is relatively simple at the phenomenological level, with rather sharp 'melting' transitions occurring. Since however the thermodynamic stability of both depends on the cooperation of a variety of non-covalent interactions which are qualitatively well understood but quantitatively difficult to assess, the full understanding and prediction of structural stability still evades us. We shall consider the effects of temperature on the different non-covalent interactions and how far these can account for protein and nucleic acid denaturation at elevated temperatures and also the cold inactivation of proteins. The latter has recently been shown to involve unsuspected complications in terms of protein conformational change. The increased stability of proteins and nucleic acids from thermophiles will be discussed. Stability is important not only in native folded proteins but also with respect to intermediate structures which occur during the folding of the newly synthesized polypeptide chain into the native, active protein. Through studies of protein folding the molecular basis of the phenomenon of temperature sensitive synthesis has been revealed. Given a stable molecular structure, its function will frequently be subject to variation with temperature. The deceptively simple temperature dependence of enzyme activity will involve the non-covalent interactions considered above for interaction between enzyme and substrate and for stability of the transition state complex. This complexity again makes the temperature dependence difficult to interpret. Further, the fact that proteins are dynamic structures is becoming recognized as an important feature factor in determining function. A balance has to be struck between on the one hand dynamic mobility which is essential for catalytic activity and on the other thermodynamic stability which holds the molecule in a potentially functional conformation under the given conditions of temperature and pressure. Readjustment of thermostability stability, as in thermophiles (or vice versa?), must also involve readjustment of dynamic mobility.(ABSTRACT TRUNCATED AT 250 WORDS)