Characterization of Ryanodine Receptors

Creative Bioarray is committed to providing clients with professional ryanodine receptor (RyR) structural and functional characterization services. We apply advanced techniques in structural, molecular, and cellular biology to help clients obtain detailed information on the expression, structure, molecular details, and function of RyRs.

Introduction

Ryanodine receptors (RyRs) are Ca²⁺ release channels present on the endoplasmic reticulum/ sarcoplasmic reticulum (ER/SR), which are involved in a series of physiological processes based on cell function, such as muscle contraction, synaptic transmission, hormone secretion, protein folding, and programmed apoptosis. These channels and inositol 1,4,5-triphosphate receptors (IP3Rs) represent two major categories of intracellular Ca²⁺ release channels. RyRs are the largest known ion channels with a total molecular weight of more than 2 MDa.

In mammals, there are three types of RyRs (RyR 1-3) widely distributed in skeletal muscle, cardiac muscle, and brain. The RyR protein complexes are the target of many pharmacological compounds, and their mechanisms are being increasingly investigated. In addition, RyR dysfunction is commonly associated with a variety of human diseases including cardiac and skeletal myopathy. Therefore, a deeper understanding of the RyR structure-function relationship will help to explain the molecular mechanisms of related diseases and facilitate the development of specific therapeutic modulators against these targets.

Fig. 1 Open RyR1 channel structure. (Meissner, 2017)

Our Services

We use cryo-EM, fluorescence resonance energy transfer (FRET), and other technologies to provide clients with detailed structural information about RyRs, as well as valuable information about expression patterns, molecular details, and other aspects. Our services include but not limited to:

• Purification and identification of RyRs.
• Structural analysis of RyRs.
• Cryo-EM studies and subnanometer resolution analysis on all three isoforms of RyRs.
• Crystal structure analysis of amino-terminal domain.
• Analysis of the closed and open pore structures.
• Identification of regulatory sites on RyR1 and RyR2 such as the FK506-binding protein (FKBP) site and sites of the Ca²⁺-free and Ca²⁺-bound forms of calmodulin (CaM).
• Measurements of conductivity and permeability of RyRs.
• Cellular and subcellular localization of RyRs.
• Interaction analysis of RyRs with other complex macromolecules, such as Ca_v1.1, Ca_v1.2, and CaM.

Applications

Our detailed characterization service has contributed to the basic biochemical, electrophysiological, and pharmacological information on RyR function, which will help clients to conduct the following research in the future:

• Study on the regulatory mechanisms of Ca²⁺ and other small molecules on RyRs
• Study on the relevance of RyR dysfunction to disease states
• Development of therapeutics for the treatment of RyRs-related diseases

Creative Bioarray focuses on the continuous optimization of structural, functional, and computational approaches to provide clients with high-quality RyR characterization services. We provide professional technical consulting to fully understand your scientific needs and develop the best experimental protocol, contributing to understanding the details of RyR isoform structure and complex physiological functions. If you are interested in our services, please contact us for more details.

Reference

1. Meissner, G. The structural basis of ryanodine receptor ion channel function. Journal of General Physiology, 2017, 149(12): 1065-1089.