Bi-directional N-terminal and Central Domain Interactions as a Critical Mechanism for Channel Gating of Ryanodine Receptor

2006 ◽  
Vol 12 (8) ◽  
pp. S164
Author(s):  
Hiroki Tateishi ◽  
Masafumi Yano ◽  
Takeshi Yamamoto ◽  
Xiaojuan Xu ◽  
Hitoshi Uchinoumi ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Channel Gating ◽  
Central Domain ◽  
Domain Interactions

Bi-directional N-terminal and central domain interactions as a critical mechanism for channel gating of ryanodine receptor

2006 ◽  
Vol 41 (6) ◽  
pp. 1070-1070
Author(s):  
H TATEISHI ◽  
M YANO ◽  
T YAMAMOTO ◽  
X XIAOJUAN ◽  
H UCHINOUMI ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Channel Gating ◽  
Central Domain ◽  
Domain Interactions

scholarly journals Role of Amino-terminal Half of the S4-S5 Linker in Type 1 Ryanodine Receptor (RyR1) Channel Gating

2011 ◽  
Vol 286 (41) ◽  
pp. 35571-35577 ◽  
Author(s):  
Takashi Murayama ◽  
Nagomi Kurebayashi ◽  
Toshiharu Oba ◽  
Hideto Oyamada ◽  
Katsuji Oguchi ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Single Channel ◽  
Signal Transmission ◽  
Channel Gating ◽  
Helical Structure ◽  
Release Channel ◽  
Amino Terminal ◽  
Molecular Events

The type 1 ryanodine receptor (RyR1) is a Ca2+ release channel found in the sarcoplasmic reticulum of skeletal muscle and plays a pivotal role in excitation-contraction coupling. The RyR1 channel is activated by a conformational change of the dihydropyridine receptor upon depolarization of the transverse tubule, or by Ca2+ itself, i.e. Ca2+-induced Ca2+ release (CICR). The molecular events transmitting such signals to the ion gate of the channel are unknown. The S4-S5 linker, a cytosolic loop connecting the S4 and S5 transmembrane segments in six-transmembrane type channels, forms an α-helical structure and mediates signal transmission in a wide variety of channels. To address the role of the S4-S5 linker in RyR1 channel gating, we performed alanine substitution scan of N-terminal half of the putative S4-S5 linker (Thr4825–Ser4829) that exhibits high helix probability. The mutant RyR1 was expressed in HEK cells, and CICR activity was investigated by caffeine-induced Ca2+ release, single-channel current recordings, and [3H]ryanodine binding. Four mutants (T4825A, I4826A, S4828A, and S4829A) had reduced CICR activity without changing Ca2+ sensitivity, whereas the L4827A mutant formed a constitutive active channel. T4825I, a disease-associated mutation for malignant hyperthermia, exhibited enhanced CICR activity. An α-helical wheel representation of the N-terminal S4-S5 linker provides a rational explanation to the observed activities of the mutants. These results suggest that N-terminal half of the S4-S5 linker may form an α-helical structure and play an important role in RyR1 channel gating.

scholarly journals The Cytoplasmic Region of Inner Helix S6 Is an Important Determinant of Cardiac Ryanodine Receptor Channel Gating

2016 ◽  
Vol 291 (50) ◽  
pp. 26024-26034 ◽  
Author(s):  
Bo Sun ◽  
Wenting Guo ◽  
Xixi Tian ◽  
Jinjing Yao ◽  
Lin Zhang ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Important Determinant ◽  
Channel Gating ◽  
Cytoplasmic Region ◽  
Receptor Channel ◽  
Cardiac Ryanodine Receptor

scholarly journals Calcium-dependent energetics of calmodulin domain interactions with regulatory regions of the Ryanodine Receptor Type 1 (RyR1)

2014 ◽  
Vol 193-194 ◽  
pp. 35-49 ◽  
Author(s):  
Rhonda A. Newman ◽  
Brenda R. Sorensen ◽  
Adina M. Kilpatrick ◽  
Madeline A. Shea
Keyword(s):  
Ryanodine Receptor ◽  
Receptor Type ◽  
Regulatory Regions ◽  
Calcium Dependent ◽  
Domain Interactions

scholarly journals Channel Gating Dependence on Pore Lining Helix Glycine Residues in Skeletal Muscle Ryanodine Receptor

2015 ◽  
Vol 290 (28) ◽  
pp. 17535-17545 ◽  
Author(s):  
Yingwu Mei ◽  
Le Xu ◽  
David D. Mowrey ◽  
Raul Mendez Giraldez ◽  
Ying Wang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Ryanodine Receptor ◽  
Channel Gating ◽  
Pore Lining

scholarly journals Molecular basis for allosteric regulation of the type 2 ryanodine receptor channel gating by key modulators

2019 ◽  
Author(s):  
Ximin Chi ◽  
Deshun Gong ◽  
Kang Ren ◽  
Gewei Zhou ◽  
Gaoxingyu Huang ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Ryanodine Receptor ◽  
Molecular Basis ◽  
Central Domain ◽  
Mechanistic Insight ◽  
Life Threatening ◽  
Cardiac Disorders ◽  
Insight Into ◽  
Receptor Channel

AbstractThe type-2 ryanodine receptor (RyR2) is responsible for releasing Ca2+ from the sarcoplasmic reticulum of cardiomyocytes, subsequently leading to muscle contraction. Here, we report four cryo-EM structures of porcine RyR2 bound to distinct modulators that collectively provide mechanistic insight into RyR2 regulation. Ca2+ alone induces a contraction of the Central domain that facilitates the dilation of S6 bundle, but is insufficient to open the pore. The small molecule agonist PCB95 helps Ca2+ to overcome the barrier for opening. FKBP12.6 induces a relaxation of the Central domain that decouples it from the S6 bundle, stabilizing RyR2 in a closed state. Caffeine locks the Central domain in a constitutively contracted state, while further addition of ATP opens the channel by strengthening the coupling between the U-motif and S6. Our study marks an important step towards mechanistic understanding of the complicated regulation of this key channel whose aberrant activity engenders life-threatening cardiac disorders.

scholarly journals Effect of sphingosylphosphorylcholine on the single channel gating properties of the cardiac ryanodine receptor

FEBS Letters ◽  
1999 ◽  
Vol 460 (3) ◽  
pp. 467-471 ◽  
Author(s):  
Akira Uehara ◽  
Midori Yasukochi ◽  
Issei Imanaga ◽  
Joshua R. Berlin
Keyword(s):  
Ryanodine Receptor ◽  
Single Channel ◽  
Channel Gating ◽  
Cardiac Ryanodine Receptor

scholarly journals Investigations of the Contribution of a Putative Glycine Hinge to Ryanodine Receptor Channel Gating

2013 ◽  
Vol 288 (23) ◽  
pp. 16671-16679 ◽  
Author(s):  
Joanne Euden ◽  
Sammy A. Mason ◽  
Cedric Viero ◽  
N. Lowri Thomas ◽  
Alan J. Williams
Keyword(s):  
Ryanodine Receptor ◽  
Striated Muscle ◽  
Transmembrane Helix ◽  
Channel Gating ◽  
Disease Process ◽  
Structural Data ◽  
Structural Basis ◽  
Detailed Knowledge ◽  
Ion Translocation ◽  
Channel Opening

Ryanodine receptor channels (RyR) are key components of striated muscle excitation-contraction coupling, and alterations in their function underlie both inherited and acquired disease. A full understanding of the disease process will require a detailed knowledge of the mechanisms and structures involved in RyR function. Unfortunately, high-resolution structural data, such as exist for K+-selective channels, are not available for RyR. In the absence of these data, we have used modeling to identify similarities in the structural elements of K+ channel pore-forming regions and postulated equivalent regions of RyR. This has identified a sequence of residues in the cytosolic cavity-lining transmembrane helix of RyR (G4864LIIDA4869 in RyR2) analogous to the glycine hinge motif present in many K+ channels. Gating in these K+ channels can be disrupted by substitution of residues for the hinge glycine. We investigated the involvement of glycine 4864 in RyR2 gating by monitoring properties of recombinant human RyR2 channels in which this glycine is replaced by residues that alter gating in K+ channels. Our data demonstrate that introducing alanine at position 4864 produces no significant change in RyR2 function. In contrast, function is altered when glycine 4864 is replaced by either valine or proline, the former preventing channel opening and the latter modifying both ion translocation and gating. Our studies reveal novel information on the structural basis of RyR gating, identifying both similarities with, and differences from, K+ channels. Glycine 4864 is not absolutely required for channel gating, but some flexibility at this point in the cavity-lining transmembrane helix is necessary for normal RyR function.

Dantrolene Stabilizes Domain–Domain Interactions within the Ryanodine Receptor in Failing Hearts

2005 ◽  
Vol 11 (9) ◽  
pp. S324
Author(s):  
Shigeki Kobayashi ◽  
Masafumi Yano ◽  
Hiroki Tateishi ◽  
Mamoru Mochizuki ◽  
Toshiyuki Noma ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Domain Interactions
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