Rag transposase mechanisms revealed by structures in Nature

Image of Schatz Lab members December 6, 2019
December 6, 2019

The Schatz Lab recently published a Nature article on the mechanism of transposase proteins. This RAG-I like transposase, Transib, is an evolutionary precursor to the RAG proteins that perform V(D)J recombination for the adaptive immune system. Transposase is a protein that uses a “cut-and-paste” method to edit the genes, meaning that it needs to recognize several DNA sites, and then cut and join them in the appropriate order. To gain a comprehensive insight into this multi-step process, the Schatz group has solved structures in different stages of this process utilizing powerful structural techniques including both X-ray crystallography and cryo-electron microscopy.

 The structure of Transib is butterfly-shaped complex that “undergoes two cycles of marked conformational changes in which the ‘wings’ of the transposase unfurl to bind substrate DNA, close to execute cleavage, open to release the flanking DNA and close again to capture and attack target DNA.” Their findings unveil the detailed mechanism of RAGs, and also provide insight into the evolution of eukaryotic transposases.

This work was published in NatureLiu et al., Structures of a RAG-like transposase during cut-and-paste transposition, Nature volume 575, pages540–544 (2019)

By Ivy Huang