scholarly journals Allostery in oligomeric receptor models

2019 ◽  
Vol 37 (3) ◽  
pp. 313-333
Author(s):  
Gregory Douglas Conradi Smith
Keyword(s):  
Algebraic Expression ◽  
Transition Diagram ◽  
Guanine Nucleotide Binding Protein ◽  
Allosteric Interactions ◽  
Equilibrium Binding ◽  
Rational Polynomial ◽  
Tree Construction ◽  
Guanine Nucleotide Binding ◽  
Receptor Dimers ◽  
Binding Curves

Abstract We show how equilibrium binding curves of receptor homodimers can be expressed as rational polynomial functions of the equilibrium binding curves of the constituent monomers, without approximation and without assuming independence of receptor monomers. Using a distinguished spanning tree construction for reduced graph powers, the method properly accounts for thermodynamic constraints and allosteric interactions between receptor monomers (i.e. conformational coupling). The method is completely general; it begins with an arbitrary undirected graph representing the topology of a monomer state-transition diagram and ends with an algebraic expression for the equilibrium binding curve of a receptor oligomer composed of two or more identical and indistinguishable monomers. Several specific examples are analysed, including guanine nucleotide-binding protein-coupled receptor dimers and tetramers composed of multiple ‘ternary complex’ monomers.

scholarly journals Allostery in oligomeric receptor models

2018 ◽  
Author(s):  
Gregory Douglas Conradi Smith
Keyword(s):  
Spanning Tree ◽  
Polynomial Functions ◽  
Allosteric Coupling ◽  
Receptor Models ◽  
Equilibrium Binding ◽  
Rational Polynomial ◽  
Tree Construction ◽  
Binding Curves

We show how equilibrium binding curves of receptor heterodimers and homodimers can be expressed as rational polynomial functions of the equilibrium binding curves of the constituent monomers, without approximation and without assuming independence of receptor monomers. Using a distinguished spanning tree construction for reduced graph powers, the method properly accounts for thermodynamic constraints and allosteric coupling between receptor monomers.

Mapping the Heart

2010 ◽  
Vol 18 (4) ◽  
pp. 6-8
Author(s):  
Stephen W. Carmichael
Keyword(s):  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
G Protein Coupled Receptors ◽  
Receptor Subtypes ◽  
Cardiac Muscle Cells ◽  
Guanine Nucleotide Binding Protein ◽  
The Common ◽  
Guanine Nucleotide Binding ◽  
First Time ◽  
G Protein Coupled

Some of the receptors on the surface of cardiac muscle cells (cardiomyocytes) mediate the response of these cells to catecholamines by causing the production of the common second messenger cyclic adenosine monophosphate (cAMP). An example of such receptors are the β1- and β2-adrenergic receptors (βARs) that are heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors. Selective stimulation of these two receptor subtypes leads to distinct physiological and pathophysiological responses, but their precise location on the surface of cardiomyocytes has not been correlated with these responses. In an ingenious combination of techniques, Viacheslav Nikolaev, Alexey Moshkov, Alexander Lyon, Michele Miragoli, Pavel Novak, Helen Paur, Martin Lohse, Yuri Korchev, Sian Harding, and Julia Gorelik have mapped the function of these receptors for the first time.

scholarly journals A novel missense variant of the GNAI3 gene and recognisable morphological characteristics of the mandibula in ARCND1

2021 ◽  
Author(s):  
Kumiko Yanagi ◽  
Noriko Morimoto ◽  
Manami Iso ◽  
Yukimi Abe ◽  
Kohji Okamura ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Morphological Characteristics ◽  
Missense Variant ◽  
Nucleotide Binding ◽  
Sequencing Analysis ◽  
Guanine Nucleotide ◽  
Guanine Nucleotide Binding Protein ◽  
Computer Tomography Scan ◽  
Novel Variant ◽  
Guanine Nucleotide Binding

AbstractAuriculocondylar syndrome (ARCND) is an autosomal monogenic disorder characterised by external ear abnormalities and micrognathia due to hypoplasia of the mandibular rami, condyle and coronoid process. Genetically, three subtypes of ARCND (ARCND1, ARCND2 and ARCND3) have been reported. To date, five pathogenic variants of GNAI3 have been reported in ARCND1 patients. Here, we report a novel variant of GNAI3 (NM_006496:c.807C>A:p.(Asn269Lys)) in a Japanese girl with micrognathia using trio-based whole exome sequencing analysis. The GNAI3 gene encodes a heterotrimeric guanine nucleotide-binding protein. The novel variant locates the guanine nucleotide-binding site, and the substitution was predicted to interfere with guanine nucleotide-binding by in silico structural analysis. Three-dimensional computer tomography scan, or cephalogram, displayed severely hypoplastic mandibular rami and fusion to the medial and lateral pterygoid plates, which have been recognised in other ARCND1 patients, but have not been described in ARCND2 and ARCND3, suggesting that these may be distinguishable features in ARCND1.

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