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J Mol Biol. 2006 Mar 3;356(4):917-27. Epub 2005 Dec 27.

Structural characterization of the RyR1-FKBP12 interaction.

Author information

1
Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. msamso@zeus.bwh.harvard.edu

Abstract

The 12 kDa FK506-binding protein (FKBP12) constitutively binds to the calcium release channel RyR1. Removal of FKBP12 using FK506 or rapamycin causes an increased open probability and an increase in the frequency of sub-conductance states in RyR1. Using cryo-electron microscopy and single-particle image processing, we have determined the 3D difference map of FKBP12 associated with RyR1 at 16 A resolution that can be fitted with the atomic model of FKBP12 in a unique orientation. This has allowed us to better define the surfaces of close apposition between FKBP12 and RyR1. Our results shed light on the role of several FKBP12 residues that had been found critical for the specificity of the RyR1-FKBP12 interaction. As predicted from previous immunoprecipitation studies, our results suggest that Gln3 participates directly in this interaction. The orientation of RyR1-bound FKBP12, with part of its FK506 binding site facing towards RyR1, allows us to propose how FK506 is involved in the dissociation of FKBP12 from RyR1.

PMID:
16405911
DOI:
10.1016/j.jmb.2005.12.023
[Indexed for MEDLINE]

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