Fatty acyl recognition and transfer by an integral membrane S -acyltransferase

Fattening up proteins Many eukaryotic proteins are modified by the attachment of lipids, and these modifications can alter how proteins interact with cellular membranes. Rana et al. present x-ray crystal structures of an integral membrane enzyme that appends a fatty acyl chain onto a cysteine residue of target proteins. The enzyme active site is situated at the membrane surface, thus explaining the enzyme's preference for substrates that are already membrane-associated. The structure of a fatty acid-like inhibitor bound within a hydrophobic cavity elucidates the mechanism for the enzyme's acyl chain specificity. Science , this issue p. eaao6326