Head-to-Head Coiled Arrangement of the Subunits of the Animal Fatty Acid Synthase Original Research Article

The role of the β-ketoacyl synthase domains in dimerization of the 2505 residue subunits of the multifunctional animal FAS has been evaluated by a combination of crosslinking and characterization of several truncated forms of the protein. Polypeptides containing only the N-terminal 971 residues can form dimers, but polypeptides lacking only the N-terminal 422 residue β-ketoacyl synthase domain cannot. FAS subunits can be crosslinked with spacer lengths as short as 6 Å, via cysteine residues engineered near the N terminus of the full-length polypeptides. The proximity of the N-terminal β-ketoacyl synthase domains and their essential role in dimerization is consistent with a revised model for the FAS in which a head-to-head arrangement of two coiled subunits facilitates functional interactions between the dimeric β-ketoacyl synthase and the acyl carrier protein domains of either subunit.