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PDBsum entry 3hsm

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protein Protein-protein interface(s) links
Signaling protein PDB id
3hsm
Jmol
Contents
Protein chains
164 a.a. *
159 a.a. *
Waters ×39
* Residue conservation analysis
PDB id:
3hsm
Name: Signaling protein
Title: Crystal structure of distal n-terminal beta-trefoil domain of ryanodine receptor type 1
Structure: Ryanodine receptor 1. Chain: a, b. Fragment: sequence database residues 1-210. Synonym: ryr-1, ryr1, skeletal muscle-type ryanodine receptor, skeletal muscle calcium release channel. Engineered: yes
Source: Oryctolagus cuniculus. Rabbit. Organism_taxid: 9986. Gene: ryr1. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.50Å     R-factor:   0.229     R-free:   0.276
Authors: F.J.Amador,S.Liu,N.Ishiyama,M.J.Plevin,A.Wilson, D.H.Maclennan,M.Ikura
Key ref:
F.J.Amador et al. (2009). Crystal structure of type I ryanodine receptor amino-terminal beta-trefoil domain reveals a disease-associated mutation "hot spot" loop. Proc Natl Acad Sci U S A, 106, 11040-11044. PubMed id: 19541610 DOI: 10.1073/pnas.0905186106
Date:
10-Jun-09     Release date:   28-Jul-09    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P11716  (RYR1_RABIT) -  Ryanodine receptor 1
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5037 a.a.
164 a.a.
Protein chain
Pfam   ArchSchema ?
P11716  (RYR1_RABIT) -  Ryanodine receptor 1
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5037 a.a.
159 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 

 

 
DOI no: 10.1073/pnas.0905186106 Proc Natl Acad Sci U S A 106:11040-11044 (2009)
PubMed id: 19541610  
 
 
Crystal structure of type I ryanodine receptor amino-terminal beta-trefoil domain reveals a disease-associated mutation "hot spot" loop.
F.J.Amador, S.Liu, N.Ishiyama, M.J.Plevin, A.Wilson, D.H.MacLennan, M.Ikura.
 
  ABSTRACT  
 
Muscle contraction and relaxation is regulated by transient elevations of myoplasmic Ca(2+). Ca(2+) is released from stores in the lumen of the sarco(endo)plasmic reticulum (SER) to initiate formation of the Ca(2+) transient by activation of a class of Ca(2+) release channels referred to as ryanodine receptors (RyRs) and is pumped back into the SER lumen by Ca(2+)-ATPases (SERCAs) to terminate the Ca(2+) transient. Mutations in the type 1 ryanodine receptor gene, RYR1, are associated with 2 skeletal muscle disorders, malignant hyperthermia (MH), and central core disease (CCD). The evaluation of proposed mechanisms by which RyR1 mutations cause MH and CCD is hindered by the lack of high-resolution structural information. Here, we report the crystal structure of the N-terminal 210 residues of RyR1 (RyR(NTD)) at 2.5 A. The RyR(NTD) structure is similar to that of the suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor (IP(3)Rsup), but lacks most of the long helix-turn-helix segment of the "arm" domain in IP(3)Rsup. The N-terminal beta-trefoil fold, found in both RyR and IP(3)R, is likely to play a critical role in regulatory mechanisms in this channel family. A disease-associated mutation "hot spot" loop was identified between strands 8 and 9 in a highly basic region of RyR1. Biophysical studies showed that 3 MH-associated mutations (C36R, R164C, and R178C) do not adversely affect the global stability or fold of RyR(NTD), supporting previously described mechanisms whereby mutations perturb protein-protein interactions.
 
  Selected figure(s)  
 
Figure 1.
Features of the RyR[NTD] structure. (A) Ribbon diagram of rabbit RyR[NTD]. The β-trefoil structure is separated into barrel (blue strands) and cap (green strands). Dotted lines represent missing residues. A top-down view is shown on the right side. (B) Sequence alignment of the distal N-terminal residues of RyR and IP[3]R isoforms. Residues highlighted in teal, yellow, and magenta denote conservation in the different layers of the barrel in both RyR[NTD] and IP[3]R[sup]. Residues in red text correspond to mutations sites in RyR1 that lead to MH or CCD, as well as to catecholaminergic polymorphic ventricular tachycardia (CPVT) and arrhythmogenic right ventricular dysplasia (ARVD2) for RyR2.
Figure 2.
Comparison of RyR[NTD] and IP[3]R[sup] structures. (A) Structural alignment of RyR[NTD] (purple) and IP[3]R[sup] (gray) structures. Topology diagram for both structures are shown in B. The 3-fold symmetry of the β-trefoil is evident, as well as differences in the arm domain. The layering of residues in the barrel is shown in C with the same color scheme as in Fig. 1B. Electrostatic surface representation is represented for IP[3]R[sup] and RyR[NTD] in D. A positive patch where mutations cluster is outlined in yellow. Residues with basic side groups found within and around the HS-loop are labeled. The structure is oriented in the top-down view described in Fig. 1A.
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22286060 M.D.Seo, S.Velamakanni, N.Ishiyama, P.B.Stathopulos, A.M.Rossi, S.A.Khan, P.Dale, C.Li, J.B.Ames, M.Ikura, and C.W.Taylor (2012).
Structural and functional conservation of key domains in InsP3 and ryanodine receptors.
  Nature, 483, 108-112.
PDB codes: 3uj0 3uj4
20934451 D.W.Song, J.G.Lee, H.S.Youn, S.H.Eom, and d.o. .H.Kim (2011).
Ryanodine receptor assembly: a novel systems biology approach to 3D mapping.
  Prog Biophys Mol Biol, 105, 145-161.  
21048710 C.C.Tung, P.A.Lobo, L.Kimlicka, and F.Van Petegem (2010).
The amino-terminal disease hotspot of ryanodine receptors forms a cytoplasmic vestibule.
  Nature, 468, 585-588.
PDB code: 2xoa
20377523 F.Wolfram, E.Morris, and C.W.Taylor (2010).
Three-dimensional structure of recombinant type 1 inositol 1,4,5-trisphosphate receptor.
  Biochem J, 428, 483-489.  
20179962 M.J.Betzenhauser, and A.R.Marks (2010).
Ryanodine receptor channelopathies.
  Pflugers Arch, 460, 467-480.  
20045464 V.Bauerová-Hlinková, E.Hostinová, J.Gasperík, K.Beck, L.Borko, F.A.Lai, A.Zahradníková, and J.Sevcík (2010).
Bioinformatic mapping and production of recombinant N-terminal domains of human cardiac ryanodine receptor 2.
  Protein Expr Purif, 71, 33-41.  
19928968 C.W.Taylor, D.L.Prole, and T.Rahman (2009).
Ca(2+) channels on the move.
  Biochemistry, 48, 12062-12080.  
19913485 P.A.Lobo, and F.Van Petegem (2009).
Crystal structures of the N-terminal domains of cardiac and skeletal muscle ryanodine receptors: insights into disease mutations.
  Structure, 17, 1505-1514.
PDB codes: 3ila 3im5 3im6 3im7
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.