8.A.11 The Immunophilin-like Prolyl:Peptidyl Isomerase Regulator (I-PPI) Family
The immunophilin-like protein TWISTED DWARF1 (TWD1/FKBP42) has been shown to physically interact with the multidrug resistance/P-glycoprotein (PGP) ATP-binding cassette transporters PGP1 and PGP19 (MDR1). Overlapping phenotypes of pgp1/pgp19 and twd1 mutant plants suggested a positive regulatory role of TWD1 in PGP-mediated export of the plant hormone auxin, which controls plant development. Bouchard et al. (2006) provided evidence at the cellular and plant levels that TWD1 controls PGP-mediated auxin transport. twd1 and pgp1/pgp19 cells showed greatly reduced export of the native auxin indole-3-acetic acid (IAA). Constitutive overexpression of PGP1 and PGP19, but not TWD1, enhanced auxin export. Coexpression of TWD1 and PGP1 in yeast and mammalian cells verified the specificity of the regulatory effect. Homologues such as the 12 kDa FKBP1 also interact with NADH dehydrogenases (TC3.D.1.8.1) and Ryanodine Receptors (RyRs). In the latter, there are 4 subunits of FKBP1 associated with the 4 large RyR subunits (Meissner 2017).
The generalized reaction catalyzed by I-PPI family members is:
Peptidylproline (omega=180) = peptidylproline (omega=0).
The peptidyl-prolyl cis-trans isomerase, FKBP1A (FKBP1; FKBP12) of 107 aas. Catalyzes the reaction: peptidylproline (omega=180) ⇌ peptidylproline (omega=0) Associates with ryanodine receptors with a subunit stoichiometry of 4:4 with the tetrameric RyRs (Meissner 2017).
FKBP1A of Homo sapiens