Structural characterization of the RyR1-FKBP12 interaction.

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.

[1]  A Leith,et al.  SPIDER and WEB: processing and visualization of images in 3D electron microscopy and related fields. , 1996, Journal of structural biology.

[2]  Joachim Frank,et al.  Cryo‐EM reveals an active role for aminoacyl‐tRNA in the accommodation process , 2002, The EMBO journal.

[3]  L. Missiaen,et al.  Characterization and mapping of the 12 kDa FK506-binding protein (FKBP12)-binding site on different isoforms of the ryanodine receptor and of the inositol 1,4,5-trisphosphate receptor. , 2001, The Biochemical journal.

[4]  S. Zissimopoulos,et al.  Interaction of FKBP12.6 with the Cardiac Ryanodine Receptor C-terminal Domain* , 2005, Journal of Biological Chemistry.

[5]  S. Fleischer,et al.  Different interactions of cardiac and skeletal muscle ryanodine receptors with FK-506 binding protein isoforms. , 1997, The American journal of physiology.

[6]  J. Zhao,et al.  Rectification of skeletal muscle ryanodine receptor mediated by FK506 binding protein. , 1995, Biophysical journal.

[7]  Wah Chiu,et al.  Two structural configurations of the skeletal muscle calcium release channel , 1996, Nature Structural Biology.

[8]  Michael Radermacher,et al.  Locations of Calmodulin and FK506-binding Protein on the Three-dimensional Architecture of the Skeletal Muscle Ryanodine Receptor* , 1997, The Journal of Biological Chemistry.

[9]  S. Fleischer,et al.  Selective Binding of FKBP12.6 by the Cardiac Ryanodine Receptor* , 1996, The Journal of Biological Chemistry.

[10]  S. Fleischer,et al.  Ryanodine sensitivity of the calcium release channel of sarcoplasmic reticulum. , 1988, Cell calcium.

[11]  L. Blayney,et al.  Physical coupling between ryanodine receptor-calcium release channels. , 2005, Journal of molecular biology.

[12]  I. Pessah,et al.  Ryanodine induces persistent inactivation of the Ca2+ release channel from skeletal muscle sarcoplasmic reticulum. , 1992, Molecular pharmacology.

[13]  M Karplus,et al.  Solution structure of FKBP, a rotamase enzyme and receptor for FK506 and rapamycin , 1991, Science.

[14]  S. Fleischer,et al.  FK-binding Protein Is Associated with the Ryanodine Receptor of Skeletal Muscle in Vertebrate Animals* , 1998, The Journal of Biological Chemistry.

[15]  R F Standaert,et al.  Atomic structure of FKBP-FK506, an immunophilin-immunosuppressant complex , 1991, Science.

[16]  P. Junankar,et al.  Subconductance states in single-channel activity of skeletal muscle ryanodine receptors after removal of FKBP12. , 1997, Biophysical journal.

[17]  T. Wagenknecht,et al.  Three-dimensional Localization of Divergent Region 3 of the Ryanodine Receptor to the Clamp-shaped Structures Adjacent to the FKBP Binding Sites* , 2003, The Journal of Biological Chemistry.

[18]  B. Xiao,et al.  Localization of the 12.6-kDa FK506-binding Protein (FKBP12.6) Binding Site to the NH2-terminal Domain of the Cardiac Ca2+ Release Channel (Ryanodine Receptor)* , 2003, The Journal of Biological Chemistry.

[19]  J. Frank,et al.  The ribosome at improved resolution: new techniques for merging and orientation refinement in 3D cryo-electron microscopy of biological particles. , 1994, Ultramicroscopy.

[20]  Niels Volkmann,et al.  Docking of atomic models into reconstructions from electron microscopy. , 2003, Methods in enzymology.

[21]  Montserrat Samsó,et al.  Internal structure and visualization of transmembrane domains of the RyR1 calcium release channel by cryo-EM , 2005, Nature Structural &Molecular Biology.

[22]  T. Wagenknecht,et al.  Three-dimensional Structure of Ryanodine Receptor Isoform Three in Two Conformational States as Visualized by Cryo-electron Microscopy* , 2000, The Journal of Biological Chemistry.

[23]  V. Sorrentino,et al.  FKBP12 associates tightly with the skeletal muscle type 1 ryanodine receptor, but not with other intracellular calcium release channels , 2001, FEBS letters.

[24]  J. Frank,et al.  Visualization of ribosome-recycling factor on the Escherichia coli 70S ribosome: Functional implications , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[25]  B. Matthews,et al.  Accurate calculation of the density of proteins. , 2000, Acta crystallographica. Section D, Biological crystallography.

[26]  N Grigorieff,et al.  Three-dimensional structure of bovine NADH:ubiquinone oxidoreductase (complex I) at 22 A in ice. , 1998, Journal of molecular biology.

[27]  P. Chacón,et al.  Multi-resolution contour-based fitting of macromolecular structures. , 2002, Journal of molecular biology.

[28]  S. Fleischer,et al.  Three Amino Acid Residues Determine Selective Binding of FK506-binding Protein 12.6 to the Cardiac Ryanodine Receptor* , 1999, The Journal of Biological Chemistry.

[29]  Jing Zhang,et al.  Location of divergent region 2 on the three-dimensional structure of cardiac muscle ryanodine receptor/calcium release channel. , 2004, Journal of molecular biology.

[30]  Morgan Huse,et al.  Crystal Structure of the Cytoplasmic Domain of the Type I TGF β Receptor in Complex with FKBP12 , 1999, Cell.

[31]  H. Erdjument-Bromage,et al.  FK506 binding protein associated with the calcium release channel (ryanodine receptor). , 1992, The Journal of biological chemistry.

[32]  M. Carson,et al.  Structure of FKBP12.6 in complex with rapamycin. , 2000, Acta crystallographica. Section D, Biological crystallography.

[33]  Stuart L. Schreiber,et al.  Structure of the FKBP12-Rapamycin Complex Interacting with Binding Domain of Human FRAP , 1996, Science.

[34]  A. Marks,et al.  The calcium release channel of sarcoplasmic reticulum is modulated by FK-506-binding protein. Dissociation and reconstitution of FKBP-12 to the calcium release channel of skeletal muscle sarcoplasmic reticulum. , 1993, The Journal of biological chemistry.

[35]  G. Meissner.  Evidence of a role for calmodulin in the regulation of calcium release from skeletal muscle sarcoplasmic reticulum. , 1986, Biochemistry.

[36]  D. H. Kim,et al.  N-terminal Region of FKBP12 Is Essential for Binding to the Skeletal Ryanodine Receptor* , 2004, Journal of Biological Chemistry.

[37]  T. Wagenknecht,et al.  Three-dimensional reconstruction of the recombinant type 3 ryanodine receptor and localization of its amino terminus , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[38]  Jun Hu,et al.  Depletion of FKBP does not affect the interaction between isolated ryanodine receptors. , 2005, Biochemical and biophysical research communications.

[39]  S. Marx,et al.  FKBP12 Binding Modulates Ryanodine Receptor Channel Gating* , 2001, The Journal of Biological Chemistry.

[40]  P. Junankar,et al.  Single channel activity of the ryanodine receptor calcium release channel is modulated by FK‐506 , 1994, FEBS letters.

[41]  S. Hamilton,et al.  Regulation of RYR1 activity by Ca(2+) and calmodulin. , 2000, Biochemistry.

[42]  P. Allen,et al.  FKBP12 Binding to RyR1 Modulates Excitation-Contraction Coupling in Mouse Skeletal Myotubes* , 2003, Journal of Biological Chemistry.

[43]  I. Pessah,et al.  Ryanodine stabilizes multiple conformational states of the skeletal muscle calcium release channel. , 1992, The Journal of biological chemistry.

[44]  D. Burkhoff,et al.  PKA Phosphorylation Dissociates FKBP12.6 from the Calcium Release Channel (Ryanodine Receptor) Defective Regulation in Failing Hearts , 2000, Cell.

[45]  J Frank,et al.  Escherichia coli 70 S ribosome at 15 A resolution by cryo-electron microscopy: localization of fMet-tRNAfMet and fitting of L1 protein. , 1998, Journal of molecular biology.

[46]  N. Grigorieff,et al.  Accurate determination of local defocus and specimen tilt in electron microscopy. , 2003, Journal of structural biology.

[47]  A. Marks,et al.  Stabilization of calcium release channel (ryanodine receptor) function by FK506-binding protein , 1994, Cell.

[48]  S. Zissimopoulos,et al.  Central domain of the human cardiac muscle ryanodine receptor does not mediate interaction with FKBP12.6 , 2007, Cell Biochemistry and Biophysics.

[49]  T. Wagenknecht,et al.  Localization of a Disease-associated Mutation Site in the Three-dimensional Structure of the Cardiac Muscle Ryanodine Receptor* , 2005, Journal of Biological Chemistry.

[50]  T. Wagenknecht,et al.  Three-dimensional Reconstruction of the Recombinant Type 2 Ryanodine Receptor and Localization of Its Divergent Region 1* , 2002, The Journal of Biological Chemistry.

[51]  T. Wagenknecht,et al.  Amino acid residues 4425-4621 localized on the three-dimensional structure of the skeletal muscle ryanodine receptor. , 2000, Biophysical journal.

[52]  D. Maclennan,et al.  Asymmetrical blockade of the Ca2+ release channel (ryanodine receptor) by 12-kDa FK506 binding protein. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[53]  Ashley M Buckle,et al.  Energetic and structural analysis of the role of tryptophan 59 in FKBP12. , 2003, Biochemistry.

[54]  J. Mccammon,et al.  Situs: A package for docking crystal structures into low-resolution maps from electron microscopy. , 1999, Journal of structural biology.

[55]  T. Molinski,et al.  Novel modulators of skeletal muscle FKBP12/calcium channel complex from Ianthella basta. Role of FKBP12 in channel gating. , 1994, The Journal of biological chemistry.

[56]  J. Ballesta,et al.  Three‐dimensional cryo‐electron microscopy localization of EF2 in the Saccharomyces cerevisiae 80S ribosome at 17.5 Å resolution , 2000, The EMBO journal.

[57]  A. P. Timerman,et al.  The calcium release channel of sarcoplasmic reticulum is modulated by FK-506 binding protein: effect of FKBP-12 on single channel activity of the skeletal muscle ryanodine receptor. , 1994, Cell calcium.

[58]  P. Caron,et al.  X-ray structure of calcineurin inhibited by the immunophilin-immunosuppressant FKBP12-FK506 complex , 1995, Cell.

[59]  M. Rossmann.  Fitting atomic models into electron-microscopy maps. , 2000, Acta crystallographica. Section D, Biological crystallography.

[60]  S. Marx,et al.  Coupled gating between individual skeletal muscle Ca2+ release channels (ryanodine receptors) , 1998, Science.

[61]  A. P. Timerman,et al.  Characterization of an Exchange Reaction between Soluble FKBP-12 and the FKBP·Ryanodine Receptor Complex , 1995, The Journal of Biological Chemistry.

[62]  Montserrat Samsó,et al.  Three-dimensional reconstruction of ryanodine receptors. , 2002, Frontiers in bioscience : a journal and virtual library.

[63]  F. Protasi,et al.  The relative position of RyR feet and DHPR tetrads in skeletal muscle. , 2004, Journal of molecular biology.