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CHRND Membrane Protein Introduction

Introduction of CHRND

CHRND, also known as acetylcholine receptor subunit delta (ACHRD), is one of the subunits of the acetylcholine receptor (AChR) and encoded by human CHRND gene. AChR, an approximately 250-kDa transmembrane protein, belongs to the cystine-loop superfamily of neurotransmitter receptors. It is a heteropentamer forming an ion pore composed of an α2βγδ subunits in the embryonic or denervated muscle, or an α2βεδ subunits in the adult muscle. The δ subunit has a large extracellular domain comprising 6 inner β-strands linked by the signature Cys-loop to 4 outer β-strands, a transmembrane domain composed of 4 α-helices that surround a central ion channel, and an intracellular domain. It is synthesized from a separate mRNA and translocated into the endoplasmic reticulum where it undergoes post-translational processing, including signal sequence cleavage and glycosylation. Following synthesis, the δ subunit presumably undergoes folding reactions, though it is not possible to measure these reactions directly.

Basic Information of CHRND
Protein Name Acetylcholine receptor subunit delta
Gene Name CHRND
Aliases ACHRD
Organism Homo sapiens (Human)
UniProt ID Q07001
Transmembrane Times 4
Length (aa) 517
Sequence MEGPVLTLGLLAALAVCGSWGLNEEERLIRHLFQEKGYNKELRPVAHKEESVDVALALTLSNLISLKEVEETLTTNVWIEHGWTDNRLKWNAEEFGNISVLRLPPDMVWLPEIVLENNNDGSFQISYSCNVLVYHYGFVYWLPPAIFRSSCPISVTYFPFDWQNCSLKFSSLKYTAKEITLSLKQDAKENRTYPVEWIIIDPEGFTENGEWEIVHRPARVNVDPRAPLDSPSRQDITFYLIIRRKPLFYIINILVPCVLISFMVNLVFYLPADSGEKTSVAISVLLAQSVFLLLISKRLPATSMAIPLIGKFLLFGMVLVTMVVVICVIVLNIHFRTPSTHVLSEGVKKLFLETLPELLHMSRPAEDGPSPGALVRRSSSLGYISKAEEYFLLKSRSDLMFEKQSERHGLARRLTTARRPPASSEQAQQELFNELKPAVDGANFIVNHMRDQNNYNEEKDSWNRVARTVDRLCLFVVTPVMVVGTAWIFLQGVYNQPPPQPFPGDPYSYNVQDKRFI

The function of CHRND Membrane Protein

The folded subunits of AChR assemble in the endoplasmic reticulum, following a defined assembly pathway, in which the first step is the formation of αδ and αε heterodimers; then they bind to each other and bind to the β subunit to form a pentamer AChR. Although each subunit of AChR contains consensus glycosylation sites, little is known about the functional role of oligosaccharide chains. The addition of sugar affects various properties of the protein, including its three-dimensional conformation, solubility, stability, and ability to be associated with other proteins. The δ subunit has three potential glycosylation sites, all of which are in the N-terminal extracellular domain. In COS cells, only two of the three potential sites of the δ subunit are glycosylated, and mutations in either of them reduces the association of the δ subunit with the α subunit to form a heterodimer, thereby affecting the intracellular assembly of the AChR and its subsequent appearance on the cell surface. Thus, glycosylation at both sites is necessary for efficient folding of δ subunit and/or for association with the α subunit to form a heterodimer. And glycosylation of the δ subunit promotes efficient folding and assembly.

CHRND Membrane Protein IntroductionFig.1 The Membrane topology of the AChR subunit. (Ramanathan, 1999.)

Application of CHRND Membrane Protein Literature

  1. Ramanathan V.K., et al. Altered glycosylation sites of the δ subunit of the acetylcholine receptor (AChR) reduce alpha delta association and receptor assembly. Journal of Biological Chemistry. 1999, 1274(29):20513-20520. PubMed ID: 10400680.

    This article suggests that glycosylation of the δ subunit at both Asn76 and Asn143 is needed for its efficient folding and/or its subsequent interaction with the α subunit.

  2. Yoshiteru A., et al. Congenital myasthenic syndrome in Japan: ethnically unique mutations in muscle nicotinic acetylcholine receptor subunits. Neuromuscular Disorders. 2015, 25(1):60-9. PubMed ID:25264167.

    This article reports six mutations in AChR subunit genes and finds that Thr284Pro in the epsilon subunit causes a slow-channel CMS.

  3. Shen X.M., et al. Mutations causing congenital myasthenia reveal principal coupling pathway in the acetylcholine receptor ε-subunit. JCI Insight. 2018, 3(2):e97826. PubMed ID:29367459.

    This article reveals εR218W reduces channel gating efficiency 338-fold and AChR expression on the cell surface 5-fold, whereas εE184K reduces channel gating efficiency 11-fold but does not alter AChR cell surface expression.

  4. Prinston J.E., et al. Ancestral reconstruction approach to acetylcholine receptor structure and function. Structure. 2017, 25(8):1295-1302. PubMed ID:28689969.

    This article resurrects humans and cartilaginous fishes ancestral β subunit and co-expresses it with human α, δ, and ɛ subunits, which shows that despite 132 substitutions, the ancestral subunit is capable of forming human/ancestral hybrid AChRs.

  5. Antoni G., et al. A multi-stage multi-design strategy provides strong evidence that the BAI3 locus is associated with early-onset venous thromboembolism. Journal of Thrombosis and Haemostasis. 2010, 8(12):2671-9. PubMed ID:20946148.

    This article suggests that the medium of BMSCs adding of NRG-1 antibody or treatment of Ras/Raf/MEK/ERK pathway inhibitors can down-regulate ACHRD expression and phosphorylation, which suggests that the Ras/Raf/MEK/ERK pathway may be involved in ACHRD expression.

CHRND Preparation Options

Membrane protein research has made significant progress over the past few years. Based on our versatile Magic™ membrane protein production platform, we could offer a range of membrane protein preparation services for worldwide customers in reconstitution forms and multiple active formats. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-CHRND antibody development services.


In the past years, Creative Biolabs has successfully produced many functional membrane proteins for our global customers. We are pleased to accelerate the development of our clients’ programs through our one-stop, custom-oriented service. For more detailed information, please feel free to contact us.

Reference

  1. Ramanathan V K, et al. (1999). Altered glycosylation sites of the δ subunit of the acetylcholine receptor (AChR) reduce alpha delta association and receptor assembly. Journal of Biological Chemistry. 1274(29), 20513-20520.

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