IS21 family transposase cleaved donor complex traps two right-handed superhelical crossings
Abstract Transposases are ubiquitous enzymes that catalyze DNA rearrangement events with broad impacts on gene expression, genome evolution, and the spread of drug-resistance in bacteria. Here, we use biochemical and structural approaches to define the molecular determinants by which IstA, a transpo...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-38071-x |
| _version_ | 1797840923958181888 |
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| author | Mercedes Spínola-Amilibia Lidia Araújo-Bazán Álvaro de la Gándara James M. Berger Ernesto Arias-Palomo |
| author_facet | Mercedes Spínola-Amilibia Lidia Araújo-Bazán Álvaro de la Gándara James M. Berger Ernesto Arias-Palomo |
| author_sort | Mercedes Spínola-Amilibia |
| collection | DOAJ |
| description | Abstract Transposases are ubiquitous enzymes that catalyze DNA rearrangement events with broad impacts on gene expression, genome evolution, and the spread of drug-resistance in bacteria. Here, we use biochemical and structural approaches to define the molecular determinants by which IstA, a transposase present in the widespread IS21 family of mobile elements, catalyzes efficient DNA transposition. Solution studies show that IstA engages the transposon terminal sequences to form a high-molecular weight complex and promote DNA integration. A 3.4 Å resolution structure of the transposase bound to transposon ends corroborates our biochemical findings and reveals that IstA self-assembles into a highly intertwined tetramer that synapses two supercoiled terminal inverted repeats. The three-dimensional organization of the IstA•DNA cleaved donor complex reveals remarkable similarities with retroviral integrases and classic transposase systems, such as Tn7 and bacteriophage Mu, and provides insights into IS21 transposition. |
| first_indexed | 2024-04-09T16:22:46Z |
| format | Article |
| id | doaj.art-580142f5ed3e4930a5687d19c91c0d29 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-09T16:22:46Z |
| publishDate | 2023-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-580142f5ed3e4930a5687d19c91c0d292023-04-23T11:22:19ZengNature PortfolioNature Communications2041-17232023-04-0114111410.1038/s41467-023-38071-xIS21 family transposase cleaved donor complex traps two right-handed superhelical crossingsMercedes Spínola-Amilibia0Lidia Araújo-Bazán1Álvaro de la Gándara2James M. Berger3Ernesto Arias-Palomo4Department of Structural & Chemical Biology, Centro de Investigaciones Biológicas Margarita Salas, CSICDepartment of Structural & Chemical Biology, Centro de Investigaciones Biológicas Margarita Salas, CSICDepartment of Structural & Chemical Biology, Centro de Investigaciones Biológicas Margarita Salas, CSICDepartment of Biophysics and Biophysical Chemistry, Johns Hopkins University School of MedicineDepartment of Structural & Chemical Biology, Centro de Investigaciones Biológicas Margarita Salas, CSICAbstract Transposases are ubiquitous enzymes that catalyze DNA rearrangement events with broad impacts on gene expression, genome evolution, and the spread of drug-resistance in bacteria. Here, we use biochemical and structural approaches to define the molecular determinants by which IstA, a transposase present in the widespread IS21 family of mobile elements, catalyzes efficient DNA transposition. Solution studies show that IstA engages the transposon terminal sequences to form a high-molecular weight complex and promote DNA integration. A 3.4 Å resolution structure of the transposase bound to transposon ends corroborates our biochemical findings and reveals that IstA self-assembles into a highly intertwined tetramer that synapses two supercoiled terminal inverted repeats. The three-dimensional organization of the IstA•DNA cleaved donor complex reveals remarkable similarities with retroviral integrases and classic transposase systems, such as Tn7 and bacteriophage Mu, and provides insights into IS21 transposition.https://doi.org/10.1038/s41467-023-38071-x |
| spellingShingle | Mercedes Spínola-Amilibia Lidia Araújo-Bazán Álvaro de la Gándara James M. Berger Ernesto Arias-Palomo IS21 family transposase cleaved donor complex traps two right-handed superhelical crossings Nature Communications |
| title | IS21 family transposase cleaved donor complex traps two right-handed superhelical crossings |
| title_full | IS21 family transposase cleaved donor complex traps two right-handed superhelical crossings |
| title_fullStr | IS21 family transposase cleaved donor complex traps two right-handed superhelical crossings |
| title_full_unstemmed | IS21 family transposase cleaved donor complex traps two right-handed superhelical crossings |
| title_short | IS21 family transposase cleaved donor complex traps two right-handed superhelical crossings |
| title_sort | is21 family transposase cleaved donor complex traps two right handed superhelical crossings |
| url | https://doi.org/10.1038/s41467-023-38071-x |
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