A protein ring
The three-dimensional structure of the yeast Tra1 protein reveals new clues about its role in regulating the activity of genes.
Inside our cells, histone proteins package and condense DNA so that it can fit into the cell nucleus. However, this also switches off the genes, since the machines that read and interpret them can no longer access the underlying DNA. Turning genes on requires specific enzymes that chemically modify the histone proteins to regain access to the DNA. This must be carefully controlled, otherwise the ‘wrong’ genes can be activated, causing undesired effects and endangering the cell.
Histone modifying enzymes often reside in large complexes of proteins. Two well-known examples are the SAGA and NuA4 complexes. Both have different roles during gene activation, but share a protein called Tra1. This protein enables SAGA and NuA4 to act on specific genes by binding to ‘activator proteins’ that are found on the DNA. Tra1 is one of the biggest proteins in the cell, but its size makes it difficult to study and, until now, its structure was unknown.
To determine the structure of Tra1, Luis Miguel Díaz-Santín and colleagues extracted the protein from baker’s yeast, and examined it using electron microscopy. The structure of Tra1 resembled a diamond ring with multiple protein domains that correspond to a band, setting and a centre stone. The structure was detailed enough that Díaz-Santín and colleagues could locate various mutations that affect the role of Tra1. These locations are likely to be direct interfaces to the ‘activator proteins’. Moreover, the study showed that Tra1 was similar to another protein that repairs damaged DNA.
These results suggest that Tra1 not only works as an activator target, but may also have a role in repairing damaged DNA and might even connect these two processes. Yeast Tra1 is also very similar to its human counterpart, which has been shown to stimulate cells to become cancerous. Further studies based on these results may help us understand how cancer begins.
Read the eLife research paper on which this eLife digest is based: “Cryo-EM structure of the SAGA and NuA4 coactivator subunit Tra1 at 3.7 angstrom resolution” (Aug 2, 2017).