6EN0

Structure of the Tn1549 transposon Integrase (aa 82-397) in complex with circular intermediate DNA (CI5-DNA)

6EN0 の概要

• エントリーDOI: 10.2210/pdb6en0/pdb
• 関連するPDBエントリー: 6EMY 6EMZ
• 分子名称: Int protein, DNA (44-MER), ... (4 entities in total)
• 機能のキーワード: transposase protein - dna complex, tyrosine recombinase, y-transposase, tn916-like conjugative transposon, antibiotic resistance transfer, recombination
• 由来する生物種: Enterococcus faecalis (Streptococcus faecalis); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 99650.88

構造登録者

Rubio-Cosials, A.,Barabas, O. (登録日: 2017-10-04, 公開日: 2018-04-04, 最終更新日: 2024-01-17)

主引用文献

Rubio-Cosials, A.,Schulz, E.C.,Lambertsen, L.,Smyshlyaev, G.,Rojas-Cordova, C.,Forslund, K.,Karaca, E.,Bebel, A.,Bork, P.,Barabas, O.
Transposase-DNA Complex Structures Reveal Mechanisms for Conjugative Transposition of Antibiotic Resistance.
Cell, 173:208-220.e20, 2018

PubMed Abstract: 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.

PubMed: 29551265
DOI: 10.1016/j.cell.2018.02.032

実験手法

X-RAY DIFFRACTION (2.8 Å)