Integration of protein functions into multi-action systems.

Abstract

Life needs multifunctional machineries as sub-systems to carry out sets of biochemical reaction pathways. Examples are, mammalian fatty acid synthetase, an integrated system of seven active sites and an acyl carrier domain, and a giant serum protein named as α 2-macroglobulin or bet- ter known as a "molecular mouse trap". The former is a highly efficient molecular factory, and the latter represents the degree of sophistication of Rube Goldberg machine at the molecular level. In the case of fatty acid synthetase, integration of seven enzymes within the short reach of 4'-phosphopanthetein of acyl carrier domain imposes a new kinetic constraints on the system. α 2-macroglobulin comprises four sequential reaction steps in a "domino" style multi-action system, starting from its encounter with a proteinase. The proteinase then cleaves a peptide bond in the "bait region" sequence of α 2-macroglobulin, which triggers spontaneous hydrolysis of the "internal thiolester", which in turn causes a massive change in the quaternary structure of α 2-macroglobulin leading to entrapment of the proteinase within the molecular achitechture of α 2-macroglobulin and formation of recetor binding sites on its surface. Determination of the rate constants of each individual step in the above sequential process is our aim to understand the molecular mechanism of the transfer of structural information and its driving force within a multi-action protein system.