A TEST OF THE JIGSAW PUZZLE MODEL FOR PROTEIN-FOLDING BY MULTIPLE METHIONINE SUBSTITUTIONS WITHIN THE CORE OF T4 LYSOZYME

To test whether the structure of a protein is determined in a manner a kin to the assembly of a jigsaw puzzle, up to 10 adjacent residues wit hin the core of T4 lysozyme were replaced by methionine. Such variants are active and fold cooperatively with progressively reduced stabilit y, The structure of a seven-methionine variant has been shown, crystal lographically, to be similar to wild type and to maintain a well order ed core. The interaction between the core residues is, therefore, not strictly comparable with the precise spatial complementarity of the pi eces of a jigsaw puzzle, Rather, a certain amount of give and take in forming the core structure is permitted, A simplified hydrophobic core sequence, imposed without genetic selection or computer-based design, is sufficient to retain native properties in a globular protein.