Recent data suggest that size polymorphism of aminoacyl tRNA synthetase is due to variable fusions of additional functional domains to a catalytic core so that, in a large synthetase, a substantial part of the polypeptide is dispensable for catalytic activity. We demonstrate here that a dispensable domain, joined to the catalytic core of a large synthetase, can activate the catalytic sites. This is shown by complementation of an activity-deficient mutant enzyme by protein fragments that contain internal deletions within the catalytic domain and are themselves devoid of activity. The complementation is dependent upon the presence of a defined segment of polypeptide that is remote in the sequence from the catalytic core. Substantial coupling has been established between dispensable and indispensable component pieces. This could be a mechanism to build efficiently large enzymes which integrate the catalytic sites with other previously shown functional roles.