2024-03-28T13:29:05Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1743732021-12-27T16:14:30Zcom_10261_41com_10261_1col_10261_294
Rubio-Cosials, Anna
Battistini, Federica
Gansen, Alexander
Cuppari, Anna
Bernadó, Pau
Orozco, Modesto
Langowski, Jörg
Tóth, Katalin
Solà, Maria
2019-01-21T07:25:31Z
2019-01-21T07:25:31Z
2018-05-22
Biophysical Journal 14(10): 2386-2396 (2018)
0006-3495
http://hdl.handle.net/10261/174373
10.1016/j.bpj.2017.11.3743
1542-0086
http://dx.doi.org/10.13039/501100004587
http://dx.doi.org/10.13039/100007678
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/501100001665
http://dx.doi.org/10.13039/501100000780
http://dx.doi.org/10.13039/501100000781
http://dx.doi.org/10.13039/501100003339
http://dx.doi.org/10.13039/501100002809
29248151
Human mitochondrial transcription factor A (TFAM) distorts DNA into a U-turn, as shown by crystallographic studies. The relevance of this U-turn is associated with transcription initiation at the mitochondrial light strand promoter (LSP). However, it has not been yet discerned whether a tight U-turn or an alternative conformation, such as a V-shape, is formed in solution. Here, single-molecule FRET experiments on freely diffusing TFAM/LSP complexes containing different DNA lengths show that a DNA U-turn is induced by progressive and cooperative binding of the two TFAM HMG-box domains and the linker between them. SAXS studies further show compaction of the protein upon complex formation. Finally, molecular dynamics simulations reveal that TFAM/LSP complexes are dynamic entities, and the HMG boxes induce the U-turn against the tendency of the DNA to adopt a straighter conformation. This tension is resolved by reversible unfolding of the linker, which is a singular mechanism that allows a flexible protein to stabilize a tight bending of DNA.
eng
closedAccess
Protein flexibility and synergy of HMG domains underlie U-turn bending of DNA by TFAM in solution
artículo