N-terminal Region of FKBP12 Is Essential for Binding to the Skeletal Ryanodine Receptor

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Structured PICO

Population

In vitro model using Triton X-100-solubilized, FKBP12-depleted rabbit skeletal sarcoplasmic reticulum vesicles

Intervention

Mutations in FKBP12 (9 specific residues and 33 various mutants)

Comparator

Wild-type FKBP12

Outcome

Binding ability to RyR1 measured by in vitro binding assay and co-immunoprecipitationsurrogate

The N-terminal regions of FKBP12 (Gln-3 and Arg-18) and Met-49 are essential for its selective binding to the skeletal ryanodine receptor (RyR1).

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May inform RyR1-selective ligand design; leaves open translation to mammalian physiology or human disease.

Lee et al. (2004) studied this question.

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