The Sec7 N-terminal regulatory domains facilitate membrane-proximal activation of the Arf1 GTPase

The cells of plants, animals and other eukaryotes are subdivided into different membrane-bound compartments. One of these compartments – called the Golgi complex – has been likened to the 'Grand Central Station' of the eukaryotic cell, because it serves as the cell’s centralized sorting compartment. Small, spherical structures called vesicles arrive at the Golgi complex from other cellular compartments, and the material within these vesicles is then sorted, packaged into new vesicles, and sent out to different destinations. Regulatory proteins are responsible for making decisions about when to turn on different incoming and outgoing pathways to or from the Golgi complex. In particular, one regulatory protein named Sec7 controls many of the outgoing vesicles that leave the Golgi complex. Sec7 is a fairly large protein and has different parts, or domains, that regulate how the protein works. It was known that two of these regulatory domains (named 'DCB' and 'HUS') were required for Sec7 to work, but it was not known what these domains actually did. Richardson et al. have now used a technique called X-ray crystallography to reveal the three-dimensional structure of the regulatory DCB and HUS domains of Sec7 from a species of yeast. The Sec7 protein has been conserved throughout evolution with few changes, and so the structure of this yeast protein is expected to be the same as that of the corresponding protein in humans. Unexpectedly, Richardson et al. discovered that DCB and HUS are not structurally separate domains and actually form a single 'DCB/HUS' domain. Biochemical experiments then showed that the DCB/HUS domain helps Sec7 work on the surface of membranes. One of the jobs of Sec7 is to insert another regulatory protein (called Arf1) into the membranes of the Golgi complex, and these new findings reveal that the DCB/HUS domain helps Sec7 overcome the challenges associated with this task. Researchers have now uncovered structural information for approximately half of the Sec7 protein, and so an important future challenge will be to reveal the structure of the remaining regulatory domains of Sec7. This achievement will help researchers to figure out how all of the parts of Sec7 work together to control how this protein makes decisions.