8sew

From Proteopedia

Jump to: navigation, search

Cryo-EM Structure of RyR1 + ADP (Local Refinement of TMD)

Structural highlights

8sew is a 4 chain structure with sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 2.89Å
Ligands:ADP, ZN
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RYR1_RABIT Calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm and thereby plays a key role in triggering muscle contraction following depolarization of T-tubules. Repeated very high-level exercise increases the open probability of the channel and leads to Ca(2+) leaking into the cytoplasm. Can also mediate the release of Ca(2+) from intracellular stores in neurons, and may thereby promote prolonged Ca(2+) signaling in the brain. Required for normal embryonic development of muscle fibers and skeletal muscle. Required for normal heart morphogenesis, skin development and ossification during embryogenesis (By similarity).[1] [2]

Publication Abstract from PubMed

The coordinated release of Ca(2+) from the sarcoplasmic reticulum (SR) is critical for excitation-contraction coupling. This release is facilitated by ryanodine receptors (RyRs) that are embedded in the SR membrane. In skeletal muscle, activity of RyR1 is regulated by metabolites such as ATP, which upon binding increase channel open probability (P(o)). To obtain structural insights into the mechanism of RyR1 priming by ATP, we determined several cryo-EM structures of RyR1 bound individually to ATP-gamma-S, ADP, AMP, adenosine, adenine, and cAMP. We demonstrate that adenine and adenosine bind RyR1, but AMP is the smallest ATP derivative capable of inducing long-range (>170 A) structural rearrangements associated with channel activation, establishing a structural basis for key binding site interactions that are the threshold for triggering quaternary structural changes. Our finding that cAMP also induces these structural changes and results in increased channel opening suggests its potential role as an endogenous modulator of RyR1 conductance.

Allosteric modulation of ryanodine receptor RyR1 by nucleotide derivatives.,Cholak S, Saville JW, Zhu X, Berezuk AM, Tuttle KS, Haji-Ghassemi O, Alvarado FJ, Van Petegem F, Subramaniam S Structure. 2023 Jul 6;31(7):790-800.e4. doi: 10.1016/j.str.2023.04.009. Epub 2023 , May 15. PMID:37192614[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Dulhunty AF, Laver DR, Gallant EM, Casarotto MG, Pace SM, Curtis S. Activation and inhibition of skeletal RyR channels by a part of the skeletal DHPR II-III loop: effects of DHPR Ser687 and FKBP12. Biophys J. 1999 Jul;77(1):189-203. PMID:10388749 doi:10.1016/S0006-3495(99)76881-5
  2. Kakizawa S, Yamazawa T, Chen Y, Ito A, Murayama T, Oyamada H, Kurebayashi N, Sato O, Watanabe M, Mori N, Oguchi K, Sakurai T, Takeshima H, Saito N, Iino M. Nitric oxide-induced calcium release via ryanodine receptors regulates neuronal function. EMBO J. 2011 Oct 28;31(2):417-28. doi: 10.1038/emboj.2011.386. PMID:22036948 doi:10.1038/emboj.2011.386
  3. Cholak S, Saville JW, Zhu X, Berezuk AM, Tuttle KS, Haji-Ghassemi O, Alvarado FJ, Van Petegem F, Subramaniam S. Allosteric modulation of ryanodine receptor RyR1 by nucleotide derivatives. Structure. 2023 Jul 6;31(7):790-800.e4. PMID:37192614 doi:10.1016/j.str.2023.04.009

Contents


PDB ID 8sew

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools