Details coming together

An atomic map of a protein complex that is implicated in both reading and repairing DNA reveals the secrets of its assembly and control.

Structure of human TFIIH with the different protein components shown in different colors, in front of a backdrop representing the DNA environment in which TFIIH functions. Image credit: Basil Greber (CC BY 4.0)

The DNA inside a cell carries the instructions it needs to survive. Living cells use many different proteins to read and maintain this store of information. For example, a group of ten proteins collectively called TFIIH is often involved in both reading and repairing the DNA. Proteins in the TFIIH complex include p52, p62, XPB and XPD.

Understanding the structure of the proteins in TFIIH could reveal much about how it works and how changes to its structure contribute to various medical conditions. Yet TFIIH is a dynamic assembly of molecules and includes many proteins, which makes examining its structure challenging. An ideal protein structure should provide an accurate map of the positions of all the atoms in a protein. Previously, it has not been possible to get this level of detail for TFIIH.

Greber et al. used an approach called cryo-electron microscopy (also called cryo-EM) to reveal the structure of TFIIH collected from human cells. The structure revealed several new details, including how p52 helps XPB attach to the rest of TFIIH, and that p62 helps to control the activity of XPD. With such a detailed structure, Greber et al. could link changes in TFIIH that are seen in different human diseases to specific parts of the complex.

Examining the atomic details of proteins can reveal a lot about how they work and the changes that occur during different diseases. These structures can also help to reveal aspects of how DNA is read and repaired, and may help to design new approaches to treat diseases in the future.