TY  - JOUR
A1  - Rubio-Cosials, Anna
A1  - Schulz, Eike C.
A1  - Lambertsen, Lotte
A1  - Smyshlyaev, Georgy
A1  - Rojas-Cordova, Carlos
A1  - Forslund, Kristoffer
A1  - Karaca, Ezgi
A1  - Bebel, Aleksandra
A1  - Bork, Peer
A1  - Barabas, Orsolya
T1  - Transposase-DNA Complex Structures Reveal Mechanisms for Conjugative Transposition of Antibiotic Resistance
JF  - Cell
N2  - Conjugative transposition drives the emergence of multidrug resistance in diverse bacterial pathogens, yet the mechanisms are poorly characterized. The Tn1549 conjugative transposon propagates resistance to the antibiotic vancomycin used for severe drug-resistant infections. Here, we present four high-resolution structures of the conserved Y-transposase of Tn1549 complexed with circular transposon DNA intermediates. The structures reveal individual transposition steps and explain how specific DNA distortion and cleavage mechanisms enable DNA strand exchange with an absolute minimum homology requirement. This appears to uniquely allow Tn916-like conjugative transposons to bypass DNA homology and insert into diverse genomic sites, expanding gene transfer. We further uncover a structural regulatory mechanism that prevents premature cleavage of the transposon DNA before a suitable target DNA is found and generate a peptide antagonist that interferes with the transposase-DNA structure to block transposition. Our results reveal mechanistic principles of conjugative transposition that could help control the spread of antibiotic resistance genes.
KW  - DNA complex
KW  - crystallography
KW  - Tn1549 transposon
KW  - Tn916-like transposon family
KW  - conjugative transposition
KW  - tyrosine recombinase
KW  - antibiotic resistance
KW  - gene transfer
KW  - vancomycin
KW  - multidrug-resistant bacteria
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227085
VL  - 173
IS  - 1
ER  -