Unknown

Dataset Information

0

Protein Flexibility and Synergy of HMG Domains Underlie U-Turn Bending of DNA by TFAM in Solution.


ABSTRACT: 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.

SUBMITTER: Rubio-Cosials A 

PROVIDER: S-EPMC6028807 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

altmetric image

Publications

Protein Flexibility and Synergy of HMG Domains Underlie U-Turn Bending of DNA by TFAM in Solution.

Rubio-Cosials Anna A   Battistini Federica F   Gansen Alexander A   Cuppari Anna A   Bernadó Pau P   Orozco Modesto M   Langowski Jörg J   Tóth Katalin K   Solà Maria M  

Biophysical journal 20171213 10


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 DN  ...[more]

Similar Datasets

| S-EPMC3210390 | biostudies-literature
| S-EPMC6321608 | biostudies-literature
| S-EPMC1300411 | biostudies-other
| S-EPMC152263 | biostudies-literature
| S-EPMC2691818 | biostudies-literature
| S-EPMC1386036 | biostudies-literature
| S-EPMC2599860 | biostudies-literature
| S-EPMC5909435 | biostudies-literature
| S-EPMC3070822 | biostudies-literature
| S-EPMC10888926 | biostudies-literature