FOXP3 recognizes microsatellites and bridges DNA through multimerization.

ABSTRACT: FOXP3 is a transcription factor that is essential for the development of regulatory T cells, a branch of T cells that suppress excessive inflammation and autoimmunity^1-5. However, the molecular mechanisms of FOXP3 remain unclear. Here we here show that FOXP3 uses the forkhead domain-a DNA-binding domain that is commonly thought to function as a monomer or dimer-to form a higher-order multimer after binding to T_nG repeat microsatellites. The cryo-electron microscopy structure of FOXP3 in a complex with T₃G repeats reveals a ladder-like architecture, whereby two double-stranded DNA molecules form the two 'side rails' bridged by five pairs of FOXP3 molecules, with each pair forming a 'rung'. Each FOXP3 subunit occupies TGTTTGT within the repeats in a manner th

SUBMITTER: Zhang W 

PROVIDER: S-EPMC10719092 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature