MuB gives a new twist to target DNA selection

Abstract

Transposition target immunity is a phenomenon observed in some DNA transposons that are able to distinguish the host chromosome from their own DNA sequence, thus avoiding self-destructive insertions. The first molecular insight into target selection and immunity mechanisms came from the study of phage Mu transposition, which uses the protein MuB as a barrier to self-insertion. MuB is an ATP-dependent non-specific DNA binding protein that regulates the activity of the MuA transposase and captures target DNA for transposition. However, a detailed mechanistic understanding of MuB functioning was hindered by the poor solubility of the MuB-ATP complexes. Here we comment on the recent discovery that MuB is an AAA+ ATPase that upon ATP binding assembles into helical filaments that coat the DNA. Remarkably, the helical parameters of the MuB filament do not match those of the bound DNA. This intriguing mismatch symmetry led us to propose a model on how MuB targets DNA for transposition, favoring DNA bending and recognition by the transposase at the filament edge. We also speculate on a different protective role of MuB during immunity, where filament stickiness could favor the condensation of the DNA into a compact state that occludes it from the transposase.

Transposition Behavior Revealed by High-Resolution Description of Pseudomonas Aeruginosa Saltovirus Integration Sites

“…A mechanism called target immunity, involving the protein MuB, prevents insertions in copies of the Mu genome [ 18 , 19 , 20 ]. The formation of MuB helical filaments in the process of transposition may protect the Mu DNA from self-insertion [ 21 ]. In the absence of such a mechanism, virion production would be significantly impaired since the viral genome (37 kb) integrating into the E. coli K-12 chromosome (4.6 Mb) during replication may eventually represents more than 50% of the total DNA.…”

Target DNA bending by the Mu transpososome promotes careful transposition and prevents its reversal

“…We propose that transposition is repressed by default except in the presence of DNA bound by target selection proteins. For Mu, target selection is driven by the distribution of MuB protein, whose reported biochemical activities appear at first glance paradoxical (reviewed in Dramićanin and Ramón-Maiques, 2013 ). MuB forms filaments along dsDNA in the presence of ATP ( Maxwell et al, 1987 ; Mizuno et al, 2013 ), and binds the C-terminal region of MuA ( Wu and Chaconas, 1994 ).…”