scholarly journals Triple Arginines as Molecular Determinants for Pentameric Assembly of the Intracellular Domain of 5-HT3A Receptors

2019 ◽  
Author(s):  
Akash Pandhare ◽  
Elham Pirayesh ◽  
Antonia G. Stuebler ◽  
Michaela Jansen
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Amino Acid ◽  
Drug Dependence ◽  
Structural Features ◽  
Amino Acid Substitutions ◽  
Intracellular Domain ◽  
Molecular Determinants ◽  
Nausea And Emesis ◽  
Post Operative Nausea

ABSTRACTSerotonin type 3A receptors (5-HT3ARs) are cation-conducting homo-pentameric ligand-gated ion channels (pLGICs) also known as the Cys-loop superfamily in eukaryotes. 5-HT3Rs are found in the peripheral and central nervous system, and they are targets for drugs used to treat anxiety, drug dependence, schizophrenia, as well as chemotherapy-induced and post-operative nausea and emesis. Decades of research of Cys-loop receptors have identified motifs in both the extracellular and transmembrane domains that mediate pentameric assembly. Those efforts have largely ignored the most diverse domain of these channels, the intracellular domain (ICD). Here we identify molecular determinants inside the ICD for pentameric assembly by first identifying the segments contributing to pentamerization using deletion constructs, and remarkably by making a small number of defined amino acid substitutions. Our work provides direct experimental evidence for the contribution of three arginines, previously implicated in governing the low conductance of 5-HT3ARs, in structural features such as pentameric assembly.

scholarly journals Triple arginines as molecular determinants for pentameric assembly of the intracellular domain of 5-HT3A receptors

2019 ◽  
Vol 151 (9) ◽  
pp. 1135-1145 ◽  
Author(s):  
Akash Pandhare ◽  
Elham Pirayesh ◽  
Antonia G. Stuebler ◽  
Michaela Jansen
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Amino Acid ◽  
Postoperative Nausea ◽  
Structural Features ◽  
Amino Acid Substitutions ◽  
Intracellular Domain ◽  
Molecular Determinants ◽  
Nausea And Emesis ◽  
Type 3

Serotonin type 3 receptors (5-HT3Rs) are cation-conducting pentameric ligand-gated ion channels and members of the Cys-loop superfamily in eukaryotes. 5-HT3Rs are found in the peripheral and central nervous system, and they are targets for drugs used to treat anxiety, drug dependence, and schizophrenia, as well as chemotherapy-induced and postoperative nausea and emesis. Decades of research of Cys-loop receptors have identified motifs in both the extracellular and transmembrane domains that mediate pentameric assembly. Those efforts have largely ignored the most diverse domain of these channels, the intracellular domain (ICD). Here we identify molecular determinants within the ICD of serotonin type 3A (5-HT3A) subunits for pentameric assembly by first identifying the segments contributing to pentamerization using deletion constructs of, and finally by making defined amino acid substitutions within, an isolated soluble ICD. Our work provides direct experimental evidence for the contribution of three intracellular arginines, previously implicated in governing the low conductance of 5-HT3ARs, in structural features such as pentameric assembly.

scholarly journals Amino acid substitutions within the heptad repeat domain 1 of murine coronavirus spike protein restrict viral antigen spread in the central nervous system

Virology ◽  
2003 ◽  
Vol 312 (2) ◽  
pp. 369-380 ◽  
Author(s):  
Jean C Tsai ◽  
Linda de Groot ◽  
Josefina D Pinon ◽  
Kathryn T Iacono ◽  
Joanna J Phillips ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Amino Acid ◽  
Viral Antigen ◽  
Spike Protein ◽  
Heptad Repeat ◽  
Amino Acid Substitutions ◽  
Repeat Domain ◽  
The Central Nervous System ◽  
Murine Coronavirus

Vasopressin analogues with effect on central nervous system: Synthesis and biological properties

1983 ◽  
Vol 48 (10) ◽  
pp. 2862-2873 ◽  
Author(s):  
František Brtník ◽  
Ivan Krejčí ◽  
Běla Kupková ◽  
Pavel Hrbas ◽  
Jana Škopková ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Amino Acid ◽  
Passive Avoidance ◽  
Biological Properties ◽  
Passive Avoidance Test ◽  
System Synthesis ◽  
Avoidance Test ◽  
Vasopressin Analogues

Synthesis of four vasopressin analogues which do not contain the glycinamine residue in position 9 and have a basic non-coded amino acid in position 8 is described. All the analogues exhibit very low endocrine activities and are effective in the passive avoidance test.

scholarly journals Capillary-Zone Electrophoretic Analyses of the Proteins and Amino Acid Components in Cerebrospinal Fluid of Central Nervous System Diseases.

1993 ◽  
Vol 16 (10) ◽  
pp. 949-952 ◽  
Author(s):  
Atsushi HIRAOKA ◽  
Isao MIURA ◽  
Munekazu HATTORI ◽  
Itaru TOMINAGA ◽  
Sachiko MACHIDA
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Amino Acid ◽  
Nervous System Diseases ◽  
Central Nervous System Diseases ◽  
Capillary Zone

scholarly journals Amino acid sequence of the encephalitogenic basic protein from human myelin

1971 ◽  
Vol 123 (1) ◽  
pp. 57-67 ◽  
Author(s):  
P. R. Carnegie
Keyword(s):  
Amino Acids ◽  
Central Nervous System ◽  
Nervous System ◽  
Amino Acid ◽  
Basic Protein ◽  
Structure And Function ◽  
Autoimmune Encephalomyelitis ◽  
The Central Nervous System ◽  
And Function ◽  
Experimental Autoimmune

Myelin from the central nervous system contains an unusual basic protein, which can induce experimental autoimmune encephalomyelitis. The basic protein from human brain was digested with trypsin and other enzymes and the sequence of the 170 amino acids was determined. The localization of the encephalitogenic determinants was described. Possible roles for the protein in the structure and function of myelin are discussed.

scholarly journals The oligodendrocyte-myelin glycoprotein belongs to a distinct family of proteins and contains the HNK-1 carbohydrate.

1990 ◽  
Vol 110 (2) ◽  
pp. 471-479 ◽  
Author(s):  
D D Mikol ◽  
J R Gulcher ◽  
K Stefansson
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Amino Acid ◽  
Terminal Segment ◽  
Platelet Glycoprotein ◽  
Glycoprotein Ib ◽  
Attachment Sites ◽  
Initial Adhesion ◽  
The Central Nervous System ◽  
Oligodendrocyte Myelin Glycoprotein

The complete primary structure of the human oligodendrocyte-myelin glycoprotein (OMgp), a glycophospholipid-linked membrane protein of oligodendrocytes and central nervous system myelin, has been determined. The deduced amino acid sequence predicts a polypeptide of 433 amino acids which includes a 17-amino acid leader sequence. OMgp consists of four domains: (a) a short cysteine-rich motif at the NH2 terminus; (b) a series of tandem leucine-rich repeats (LRs) present in several other proteins where they may play roles in adhesion; (c) a serine/threonine-rich region that contains probable attachment sites for O-linked carbohydrates; and (d) a hydrophobic COOH-terminal segment that is likely to be cleaved concomitant with the attachment of lipid during biosynthesis of OMgp. OMgp shares the first three of its four domains with the platelet glycoprotein Ib, which is responsible for the initial adhesion of platelets to the exposed subendothelium during hemostasis. Together with glycoprotein Ib and several other proteins, OMgp belongs to a family of proteins that contain both an NH2-terminal cysteine-rich motif and an adjacent series of LRs. In addition, we report that a subpopulation of OMgp molecules contains the HNK-1 carbohydrate, which has been shown to mediate interactions among cells in the central nervous system.

Neurogenic and antineurogenic effects from modifications at the Notch locus

Development ◽  
1990 ◽  
Vol 109 (1) ◽  
pp. 167-175 ◽  
Author(s):  
J. Palka ◽  
M. Schubiger ◽  
H. Schwaninger
Keyword(s):  
Nervous System ◽  
Amino Acid ◽  
Distinctive Feature ◽  
Single Amino Acid ◽  
Amino Acid Substitutions ◽  
Wild Type ◽  
Significant Extent ◽  
Notch Protein ◽  
Notch Locus ◽  
Mother Cells

The best studied mutations at the Notch locus produce a neurogenic phenotype, with a massive overgrowth of the nervous system at the expense of epidermis. We report here that, in the development of the adult peripheral nervous system, the Abruptex alleles of Notch have the opposite phenotype, namely an underproduction of sensory organs or sensilla. This arises primarily not from an arrest of the lineages that produce sensilla, from the degeneration of sensillar cells, or from the transformation into neurons of cells that normally secrete the cuticular components of a sensillum (as can happen in Notch alleles). Rather, our evidence argues strongly that the sensillar mother cells never form. This implies that the Notch protein plays a role in the process that first generates a difference between sensillar mother cells and ordinary epidermal cells. The number of sensilla formed on the wing of flies carrying multiple doses of Notch+ is virtually the same as that of wild type, i.e. the Abruptex phenotype is not reproduced to any significant extent. This suggests that the single amino acid substitutions that occur in Abruptex mutants confer on the protein some functionally distinctive feature, possibly more powerful intermolecular binding or altered stability.

scholarly journals Activity of D-amino acid oxidase is widespread in the human central nervous system

2014 ◽  
Vol 6 ◽  
Author(s):  
Jumpei Sasabe ◽  
Masataka Suzuki ◽  
Nobuaki Imanishi ◽  
Sadakazu Aiso
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Amino Acid ◽  
Acid Oxidase ◽  
Human Central Nervous System ◽  
Amino Acid Oxidase
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