A look into DGAT1 through the EM lenses

With the advent of modern detectors and robust structure solution pipeline, cryogenic electron microscopy has recently proved to be game changer in structural biology. Membrane proteins are challenging targets for structural biologists. This minireview focuses a membrane embedded triglyceride synthesizing machine, DGAT1. Decades of research had built the foundational knowledge on this enzyme's activity. However, recently solved cryo-EM structures of this enzyme, in apo and bound form, has provided critical mechanistic insights. The flipping of the catalytic histidine is critical of enzyme catalysis. The structures explain why the enzyme has preference to long fatty acyl chains over the short forms. [Display omitted] •The swapping of structural elements between protomers leads to the stabilization of the human DGAT1 dimer.•The structure of the substrate-bound form reveals the preference for long-chain acyl CoAs over their shorter counterparts.•The lateral gate provides the second substrate, DAG, access to the reaction chamber.