Depolarization of the external membrane of cardiac and skeletal muscle results in release of Ca2+ from intracellular stores, which in turn, elicits contraction. The voltage sensor of the external membrane is the dihydropyridine receptor (DHPR) and the protein responsible for Ca2+ release is the Ca2+ release channel of sarcoplasmic reticulum, also know as the ryanodine receptor (RyR). The mechanism by which DHPRs open RyR and elicit contraction is unknown, but recent findings suggest that a specific segment of the DHPR may be directly connected to RyR. Imperatoxin A (IpTxa), a 33 amino acid scorpion toxin that opens RyR with high affinity, may provide information regarding the exact amino acids involved in the interaction between DHPR and RyR and the nature of the reaction involved. The binding of IpTxa is displaced by a 22 amino acid segment of the DHPR and both, IpTxa and the DHPR segment loose their capacity to open RyR when a Thr (in IpTxa) or Ser (in DHPR) is replaced by a negatively-charged amino acid. Thus, IpTxa open Ryr in a manner which is similar to the natural DHPR-RyR interaction. Elucidation of the three-dimensional structure of IpTxa will add significantly to our understanding of how DHPR interacts with RyR.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
2P41RR002301-16
Application #
6309182
Study Section
Project Start
2000-04-15
Project End
2005-02-28
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
16
Fiscal Year
2000
Total Cost
$7,533
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Travers, Timothy; López, Cesar A; Van, Que N et al. (2018) Molecular recognition of RAS/RAF complex at the membrane: Role of RAF cysteine-rich domain. Sci Rep 8:8461
Thomas, Nathan E; Wu, Chao; Morrison, Emma A et al. (2018) The C terminus of the bacterial multidrug transporter EmrE couples drug binding to proton release. J Biol Chem 293:19137-19147
Assadi-Porter, Fariba M; Radek, James; Rao, Hongyu et al. (2018) Multimodal Ligand Binding Studies of Human and Mouse G-Coupled Taste Receptors to Correlate Their Species-Specific Sweetness Tasting Properties. Molecules 23:
Wijayatunga, Nadeeja N; Sams, Valerie G; Dawson, John A et al. (2018) Roux-en-Y gastric bypass surgery alters serum metabolites and fatty acids in patients with morbid obesity. Diabetes Metab Res Rev 34:e3045
Assadi-Porter, Fariba M; Reiland, Hannah; Sabatini, Martina et al. (2018) Metabolic Reprogramming by 3-Iodothyronamine (T1AM): A New Perspective to Reverse Obesity through Co-Regulation of Sirtuin 4 and 6 Expression. Int J Mol Sci 19:
Dominguez, Eddie; Zarnowski, Robert; Sanchez, Hiram et al. (2018) Conservation and Divergence in the Candida Species Biofilm Matrix Mannan-Glucan Complex Structure, Function, and Genetic Control. MBio 9:
Franco, Aldo; Dovell, Sanaz; Möller, Carolina et al. (2018) Structural plasticity of mini-M conotoxins - expression of all mini-M subtypes by Conus regius. FEBS J 285:887-902
Wales, Jessica A; Chen, Cheng-Yu; Breci, Linda et al. (2018) Discovery of stimulator binding to a conserved pocket in the heme domain of soluble guanylyl cyclase. J Biol Chem 293:1850-1864
Selen Alpergin, Ebru S; Bolandnazar, Zeinab; Sabatini, Martina et al. (2017) Metabolic profiling reveals reprogramming of lipid metabolic pathways in treatment of polycystic ovary syndrome with 3-iodothyronamine. Physiol Rep 5:
Mong, Surin K; Cochran, Frank V; Yu, Hongtao et al. (2017) Heterochiral Knottin Protein: Folding and Solution Structure. Biochemistry 56:5720-5725

Showing the most recent 10 out of 613 publications