WordNet
- any of a large group of nitrogenous organic compounds that are essential constituents of living cells; consist of polymers of amino acids; essential in the diet of animals for growth and for repair of tissues; can be obtained from meat and eggs and milk and legumes; "a diet high in protein"
- a simple compound whose molecules can join together to form polymers
- a unit of force equal to the force exerted by gravity; used to indicate the force to which a body is subjected when it is accelerated (同)gee, g-force
- the 7th letter of the Roman alphabet (同)g
PrepTutorEJDIC
- 蛋白(たんばく)質
- 単量体(異種の分子と反応し重合体を構成する)
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- 1. ペプチドホルモンのシグナル伝達および調節 peptide hormone signal transduction and regulation
- 2. 先天性性腺刺激ホルモン放出ホルモン欠乏症（特発性低ゴナドトロピン性性腺機能低下） congenital gonadotropin releasing hormone deficiency idiopathic hypogonadotropic hypogonadism
- 3. 血小板生物学 platelet biology
- 4. 正常思春期 normal puberty
- 5. セクレチン secretin
English Journal
- Structural biology of glycoprotein hormones and their receptors: Insights to signaling.
- Jiang X, Dias JA, He X.Author information EMD Serono Research & Development Institute, Billerica, MA 01821, United States. Electronic address: xuliang.jiang@emdserono.com.AbstractThis article reviews the progress made in the field of glycoprotein hormones (GPH) and their receptors (GPHR) by several groups of structural biologists including ourselves aiming to gain insight into GPH signaling mechanisms. The GPH family consists of four members, with follicle-stimulating hormone (FSH) being the prototypic member. GPH members belong to the cystine-knot growth factor superfamily, and their receptors (GPHR), possessing unusually large N-terminal ectodomains, belong to the G-protein coupled receptor Family A. GPHR ectodomains can be divided into two subdomains: a high-affinity hormone binding subdomain primarily centered on the N-terminus, and a second subdomain that is located on the C-terminal region of the ectodomain that is involved in signal specificity. The two subdomains unexpectedly form an integral structure comprised of leucine-rich repeats (LRRs). Following the structure determination of hCG in 1994, the field of FSH structural biology has progressively advanced. Initially, the FSH structure was determined in partially glycosylated free form in 2001, followed by a structure of FSH bound to a truncated FSHR ectodomain in 2005, and the structure of FSH bound to the entire ectodomain in 2012. Comparisons of the structures in three forms led a proposal of a two-step monomeric receptor activation mechanism. First, binding of FSH to the FSHR high-affinity hormone-binding subdomain induces a conformational change in the hormone to form a binding pocket that is specific for a sulfated-tyrosine found as sTyr 335 in FSHR. Subsequently, the sTyr is drawn into the newly formed binding pocket, producing a lever effect on a helical pivot whereby the docking sTyr provides as the 'pull & lift' force. The pivot helix is flanked by rigid LRRs and locked by two disulfide bonds on both sides: the hormone-binding subdomain on one side and the last short loop before the first transmembrane helix on the other side. The lift of the sTyr loop frees the tethered extracellular loops of the 7TM domain, thereby releasing a putative inhibitory influence of the ectodomain, ultimately leading to the activating conformation of the 7TM domain. Moreover, the data lead us to propose that FSHR exists as a trimer and to present an FSHR activation mechanism consistent with the observed trimeric crystal form. A trimeric receptor provides resolution of the enigmatic, but important, biological roles played by GPH residues that are removed from the primary FSH-binding site, as well as several important GPCR phenomena, including negative cooperativity and asymmetric activation. Further reflection pursuant to this review process revealed additional novel structural characteristics such as the identification of a 'seat' sequence in GPH. Together with the 'seatbelt', the 'seat' enables a common heteodimeric mode of association of the common α subunit non-covalently and non-specifically with each of the three different β subunits. Moreover, it was possible to establish a dimensional order that can be used to estimate LRR curvatures. A potential binding pocket for small molecular allosteric modulators in the FSHR 7TM domain has also been identified.
- Molecular and cellular endocrinology.Mol Cell Endocrinol.2014 Jan 25;382(1):424-51. doi: 10.1016/j.mce.2013.08.021. Epub 2013 Aug 31.
- This article reviews the progress made in the field of glycoprotein hormones (GPH) and their receptors (GPHR) by several groups of structural biologists including ourselves aiming to gain insight into GPH signaling mechanisms. The GPH family consists of four members, with follicle-stimulating hormon
- PMID 24001578
- Hetero-bivalent GLP-1/Glibenclamide for Targeting Pancreatic β-Cells.
- Hart NJ, Chung WJ, Weber C, Ananthakrishnan K, Anderson M, Patek R, Zhang Z, Limesand SW, Vagner J, Lynch RM.Author information Department of Physiological Sciences, University of Arizona, 1656 E. Mabel St., Tucson, AZ 85721 (USA).AbstractG protein-coupled receptor (GPCR) cell signalling cascades are initiated upon binding of a specific agonist ligand to its cell surface receptor. Linking multiple heterologous ligands that simultaneously bind and potentially link different receptors on the cell surface is a unique approach to modulate cell responses. Moreover, if the target receptors are selected based on analysis of cell-specific expression of a receptor combination, then the linked binding elements might provide enhanced specificity of targeting the cell type of interest, that is, only to cells that express the complementary receptors. Two receptors whose expression is relatively specific (in combination) to insulin-secreting pancreatic β-cells are the sulfonylurea-1 (SUR1) and the glucagon-like peptide-1 (GLP-1) receptors. A heterobivalent ligand was assembled from the active fragment of GLP-1 (7-36 GLP-1) and glibenclamide, a small organic ligand for SUR1. The synthetic construct was labelled with Cy5 or europium chelated in DTPA to evaluate binding to β-cells, by using fluorescence microscopy or time-resolved saturation and competition binding assays, respectively. Once the ligand binds to β-cells, it is rapidly capped and presumably removed from the cell surface by endocytosis. The bivalent ligand had an affinity approximately fivefold higher than monomeric europium-labelled GLP-1, likely a result of cooperative binding to the complementary receptors on the βTC3 cells. The high-affinity binding was lost in the presence of either unlabelled monomer, thus demonstrating that interaction with both receptors is required for the enhanced binding at low concentrations. Importantly, bivalent enhancement was accomplished in a cell system with physiological levels of expression of the complementary receptors, thus indicating that this approach might be applicable for β-cell targeting in vivo.
- Chembiochem : a European journal of chemical biology.Chembiochem.2014 Jan 3;15(1):135-45. doi: 10.1002/cbic.201300375. Epub 2013 Nov 20.
- G protein-coupled receptor (GPCR) cell signalling cascades are initiated upon binding of a specific agonist ligand to its cell surface receptor. Linking multiple heterologous ligands that simultaneously bind and potentially link different receptors on the cell surface is a unique approach to modulat
- PMID 24259278
- Regulation of Beta-2-Adrenergic Receptor Function by Conformationally Selective Single-domain Intrabodies.
- Staus DP, Wingler LM, Strachan RT, Rasmussen SG, Pardon E, Ahn S, Steyaert J, Kobilka BK, Lefkowitz RJ.Author information Duke University Medical Center;AbstractThe biological activity induced by ligand binding to orthosteric or allosteric sites on a GPCR is mediated by stabilization of specific receptor conformations. In the case of the β2 adrenergic receptor, these ligands are generally small molecule agonists or antagonists. However, recently a monomeric single domain antibody (nanobody) from the Camelid family was found to allosterically bind and stabilize an active conformation of the β2 adrenergic receptor (β2AR). Here we set out to study the functional interaction of 18 related nanobodies with the β2 adrenergic receptor to investigate their roles as novel tools for studying GPCR biology. Our studies revealed several sequence related nanobody families with preferences for active (agonist occupied) or inactive (antagonist occupied) receptors. Flow cytometry analysis indicates that all nanobodies bind to epitopes displayed on the intracellular receptor surface, therefore we transiently expressed them intracellularly (intrabodies) to test their effects on β2AR-dependent signaling Conformational specificity was preserved after intrabody conversion as demonstrated by the ability for the intracellularly expressed nanobodies to selectively bind agonist or antagonist-occupied receptors. When expressed as intrabodies inhibited G-protein activation (cyclic AMP accumulation), GRK-mediated receptor phosphorylation, β-arrestin recruitment, and receptor internalization to varying extents. These functional effects were likely due to either steric blockade of downstream effector (Gs, β-arrestin, GRK) interactions or stabilization of specific receptor conformations which do not support effector coupling. Together these findings strongly implicate nanobody-derived intrabodies as novel tools to study GPCR biology.
- Molecular pharmacology.Mol Pharmacol.2013 Dec 6. [Epub ahead of print]
- The biological activity induced by ligand binding to orthosteric or allosteric sites on a GPCR is mediated by stabilization of specific receptor conformations. In the case of the β2 adrenergic receptor, these ligands are generally small molecule agonists or antagonists. However, recently a monomeri
- PMID 24319111
Japanese Journal
- Cfs1p, a Novel Membrane Protein in the PQ-Loop Family, Is Involved in Phospholipid Flippase Functions in Yeast
- G3 : genes, genomes, genetics 7(1), 179-192, 2017-01
- NAID 120005981408
- The Open Form Inducer Approach for Structure-Based Drug Design
- PLOS ONE 11(11), e0167078, 2016-11-28
- NAID 120006221139
- Gateway Vectors for Simultaneous Detection of Multiple Protein−Protein Interactions in Plant Cells Using Bimolecular Fluorescence Complementation
- PLOS ONE 11(8), 2016-08-04
- NAID 120005997754
Related Links
- Abstract G protein-coupled receptors mediate biological signals by stimulating nucleotide exchange in heterotrimeric G proteins (Gαβγ). Receptor dimers have been proposed as the functional unit responsible for ...
- Abstract G protein-coupled receptors (GPCRs) respond to a diverse array of ligands, mediating cellular responses to hormones and neurotransmitters, as well as the senses of smell and taste. The structures of the ...
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| リンク元 | 「単量体Gタンパク」 |
| 関連記事 | 「G」「monomer」「G protein」「Gd」「monomeric」 |
「単量体Gタンパク」
「G」
「monomer」
「G protein」
「Gd」
「monomeric」
- 単量体の
- 関
- monomer