STRUCTURE-FUNCTION-RELATIONSHIPS OF THE YEAST FATTY-ACID SYNTHASE - NEGATIVE-STAIN, CRYOELECTRON MICROSCOPY, AND IMAGE-ANALYSIS STUDIES OF THE END VIEWS OF THE STRUCTURE

The yeast fatty acid synthase (M(r) = 2.5 x 10(6)) is organized in an alpha-6-beta-6 complex. In these studies, the synthase structure has been examined by negative-stain and cryoelectron microscopy. Side and end views of the structure indicate that the molecule, shaped similar to a prolate ellipsoid, has a high-density band of protein bisecting its major axis. Stained and frozen-hydrated average images of the end views show an excellent concordance and a hexagonal ring having three each alternating egg- and kidney-shaped features with low-protein-density protrusions extending outward from the egg-shaped features. Images also show that the barrel-like structure is not hollow but has a Y-shaped central core, which appears to make contact with the three egg-shaped features. Numerous side views of the structure give good evidence that the beta-subunits have an archlike shape. We propose a model for the synthase that has point-group symmetry 32 and six equivalent sites of fatty acid synthesis. The protomeric unit is alpha-2-beta-2. The ends of each of the two archlike beta-subunits interact with opposite sides of the two dichotomously arranged disclike alpha-subunits. Three such protomeric units form the ring. We propose that the six fatty acid synthesizing centers are composed of two complementary half-alpha subunits and a beta-subunit, an arrangement having all the partial activities of the multifunctional enzyme required for fatty acid synthesis.