Propagation of conformational instability in FK506-binding protein FKBP12.

ABSTRACT: FKBP12 is the archetype of the FK506 binding domains that define the family of FKBP proteins which participate in the regulation of various distinct physiological signaling processes. As the drugs FK506 and rapamycin inhibit many of these FKBP proteins, there is need to develop therapeutics which exhibit selectivity within this family. The long β₄-β₅ loop of the FKBP domain is known to regulate transcriptional activity for the steroid hormone receptors and appears to participate in regulating calcium channel activity for the cardiac and skeletal muscle ryanodine receptors. The β₄-β₅ loop of FKBP12 has been shown to undergo extensive conformational dynamics, and here we report hydrogen exchange measurements for a series of mutational variants in t

SUBMITTER: LeMaster DM 

PROVIDER: S-EPMC10939819 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature