Dynamics-modulated biological activity of transforming growth factor β3

Abstract

Transforming growth factor β3 (TGF-β3) is an important mediator of growth, maintenance, and repair processes in human cells. Internal dynamic properties have been derived from 15N NMR relaxation data and mapped onto the spatial structure of TGF-β3. The pattern of internal dynamics in the structure identifies potential "hot spots" of binding free energy and reveals the importance of conformational entropy in the interaction of TGF-β3 with the receptors. The observed internal dynamics set TGF-β3 apart from other TGF-β3 isoforms, with which it shares the same fold. These findings may explain functional differences among the various TGF-β isoforms and thus prove essential in the search for related therapeutic agents.