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Updated: Jul 14, 2026

Structure and Coordination Determination of Peptide-metal Complexes Using 1D and 2D 1H NMR
Published on: December 16, 2013
Multimer formation by FKBP-12: roles for cysteine 23 and phenylalanine 36
Barbara Schories1, Thomas E Nelson, David C Sane
1Section of Cardiology, Department of Internal Medicine and Wake Forest University School of Medicine, Winston-Salem, NC 27157-1045, USA.
Abstract:
FKBP-12 mediates the immunosuppressive actions of FK506 and rapamycin, and modulates the activities of the ryanodine, IP3 and type 1 TGF-ss receptors. Additionally, FKBP-12 possesses cis-trans peptidylprolyl isomerase (rotamase) activity. We have discovered that recombinant FKBP-12 readily forms a dimer and a small amount of trimer under nonreducing conditions. A mutant with substitution at the sole cysteine residue of FKBP-12 (C23S) did not form dimers or trimers. Using mutants with 5% or less rotamase activity, the formation of dimers was independent of enzymatic activity. The formation of trimers was abrogated by a F36Y substitution, even though dimer formation was preserved. Dimers were also observed with native FKBP-12 that was detached from rabbit skeletal muscle ryanodine receptors using FK590. The multimers of FKBP-12 could interact with molecular targets distinctly from the FKBP-12 monomer, for example, by facilitating the assembly of multimeric receptors or coordinating the activity of receptor subunits.
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