Congenital heart disease missense mutations in the TBX5 DNA-binding domain alter thermal stability and DNA-binding affinity.

ABSTRACT: Missense mutations can alter the biochemical properties of proteins, including stability, structure, and function, potentially contributing to the development of multiple human diseases. Mutations in TBX5, a transcription factor (TF) necessary for heart development, are among the causes of congenital heart diseases (CHD). However, further research on biophysical and biochemical mechanisms is needed to understand how missense mutations in TFs alter their function in regulating gene expression. In this work, we applied in vitro and in silico approaches to understand how five missense mutations in the TBX5 T-box DNA-binding domain (I54T, M74V, I101F, R113K, and R237W) impact protein structure, thermal stability, and DNA-binding affinity to known TBX5 cognate binding sites

SUBMITTER: Rivera-Madera A 

PROVIDER: S-EPMC12132455 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature