Back to Search
Start Over
Subnanometer-resolution electron cryomicroscopy-based domain models for the cytoplasmic region of skeletal muscle RyR channel.
- Source :
- Proceedings of the National Academy of Sciences of the United States of America; 7/15/2008, Vol. 105 Issue 28, p9610-9615, 6p, 4 Diagrams
- Publication Year :
- 2008
-
Abstract
- The skeletal muscle Ca<superscript>2+</superscript> release channel (RyR1), a homotetramer, regulates the release of Ca<superscript>2+</superscript> from the sarcoplasmic reticulum to initiate muscle contraction. In this work, we have delineated the RyR1 monomer boundaries in a subnanometer-resolution electron cryomicroscopy (cryo-EM) density map. In the cytoplasmic region of each RyR1 monomer, 36 α-helices and 7 β-sheets can be resolved. A β-sheet was also identified close to the membrane-spanning region that resembles the cytoplasmic pore structures of inward rectifier K<superscript>+</superscript> channels. Three structural folds, generated for amino acids 12-565 using comparative modeling and cryo-EM density fitting, localize close to regions implicated in communication with the voltage sensor in the transverse tubules. Eleven of the 15 disease-related residues for these domains are mapped to the surface of these models. Four disease-related residues are found in a basin at the interfaces of these regions, creating a pocket in which the immunophilin FKBP12 can fit. Taken together, these results provide a structural context for both channel gating and the consequences of certain malignant hyperthermia and central core disease-associated mutations in RyR1. [ABSTRACT FROM AUTHOR]
- Subjects :
- SARCOPLASM
CRYOMICROSCOPY
MONOMERS
CYTOPLASM
AMINO acids
GENETIC mutation
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 105
- Issue :
- 28
- Database :
- Complementary Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 33399767
- Full Text :
- https://doi.org/10.1073/pnas.0803189105