ABSTRACT
Based on our theory, main triplets of amino acid residues have been discovered in cell-adhesion receptors (integrins) of marine sponges, which participate as homologies in the interface between two major immune molecules, MHC class I (MHCI) and CD8αß. They appear as homologies also in several human neural receptor heteromers and subunits. The obtained results probably mean that neural and immune receptors also utilize these structural integrin triplets to form heteromers and ion channels, which are required for a tuned and integrated intracellular and intercellular communication and a communication between cells and the extracellular matrix with an origin in sponges, the oldest multicellular animals.
ABSTRACT
The evidence for the existence of receptor heteromers opens up a new field for a better understanding of neural transmission. Based on our theory, we have discovered main triplets of amino acid residues in cell-adhesion receptors of marine sponges, which appear also as homologies in several dopamine D2 receptor heteromers of human brain. The obtained results probably mean a general molecular mechanism for receptor-receptor interactions in heteromers originated from the lowest animals (marine sponges).
Subject(s)
Aquatic Organisms/metabolism , Integrins/chemistry , Porifera/metabolism , Protein Multimerization , Receptors, Dopamine D2/chemistry , Receptors, Dopamine D2/metabolism , Amino Acid Sequence , Animals , Brain/metabolism , Evolution, Molecular , Humans , Molecular Sequence Data , Sequence AlignmentABSTRACT
Based on our theory, we have discovered main triplets of amino acid residues in cell-adhesion receptors of marine sponges, which appear also as homologies in several receptor heteromers of human brain. The obtained results strengthen our hypothesis that these triplets may "guide-and-clasp" receptor-receptor interactions.
Subject(s)
Brain/physiology , Evolution, Molecular , Geodia/genetics , Integrins/genetics , Receptors, Cell Surface/genetics , Animals , Humans , Molecular Sequence Data , Phylogeny , Receptor, Cholecystokinin B/genetics , Receptor, Fibroblast Growth Factor, Type 1/genetics , Receptor, Metabotropic Glutamate 5 , Receptor, Serotonin, 5-HT1A/genetics , Receptor, Serotonin, 5-HT1B/genetics , Receptor, Serotonin, 5-HT1D/genetics , Receptors, Adrenergic, alpha-2/genetics , Receptors, GABA-B/genetics , Receptors, Metabotropic Glutamate/genetics , Sequence Homology, Amino AcidABSTRACT
Based on our theory, we have discovered main triplets of amino acid residues in the GABAB1 receptor and several other neural receptors which seem to come from immunoglobulin chains and appear also as homologies in receptor heteromers. The obtained results strengthen our hypothesis that these triplets may "guide-and-clasp" receptor-receptor interactions playing a role, e.g., in neuroinflammation disorders.
Subject(s)
Immunoglobulin G/chemistry , Immunoglobulin M/chemistry , Models, Chemical , Amino Acid Sequence , Animals , Epitopes/chemistry , Epitopes/immunology , Humans , Immunoglobulin Heavy Chains/chemistry , Immunoglobulin Light Chains/chemistry , Neurogenic Inflammation/immunology , Neurogenic Inflammation/metabolism , Neuroimmunomodulation/genetics , Neuroimmunomodulation/immunology , Protein Interaction Domains and Motifs/immunology , Protein Multimerization/immunology , Receptors, GABA-B/chemistry , Sequence Homology, Amino AcidABSTRACT
Based on our theory, we have discovered main triplets of amino acid residues in the GABAB1 receptor and several other neural receptors, which seem to originate from toll-like receptors and appear also as homologies in receptor heteromers. The obtained results strengthen our hypothesis that these triplets may 'guide-and-clasp' receptor-receptor interactions.
Subject(s)
Receptors, Neurotransmitter/chemistry , Toll-Like Receptors/chemistry , Amino Acid Sequence , Animals , Humans , Molecular Sequence Data , Protein Subunits/chemistry , Protein Subunits/genetics , Receptor Protein-Tyrosine Kinases/chemistry , Receptor Protein-Tyrosine Kinases/genetics , Receptors, G-Protein-Coupled/chemistry , Receptors, G-Protein-Coupled/genetics , Receptors, GABA-A/chemistry , Receptors, GABA-A/genetics , Receptors, Neurotransmitter/genetics , Signal Transduction/physiology , Toll-Like Receptors/geneticsABSTRACT
Based on our theory, we point out main triplets of amino acid residues in the GABAB1 receptor, found in the central and peripheral nervous system, which seem to be critical for both receptor heterodimerization and chemokine binding. The obtained results suggest that these triplets may "guide-and-clasp" protein-protein interactions playing a role, e.g., in neuroinflammation disorders.
Subject(s)
Amino Acid Motifs , Protein Interaction Domains and Motifs/genetics , Protein Multimerization , Receptors, GABA-B/chemistry , Receptors, GABA-B/genetics , Animals , Humans , Models, Molecular , Molecular Sequence Data , Protein Binding , Protein Isoforms/chemistry , Protein Isoforms/genetics , Protein Isoforms/metabolism , Receptors, GABA-B/metabolism , Sequence AlignmentABSTRACT
Based on a mathematical approach, we deduce a set of triplet homologies that may be responsible for receptor-receptor interactions. We show how such triplets of amino acid residues and their 'teams' may be utilized to construct a kind of code that determines (and/or predicts) which receptors should or should not form heterodimers. Based on the obtained results, we propose a 'guide-and-clasp' manner for receptor-receptor interactions where 'adhesive guides' might be the triplet homologies. We also demonstrate their relevance to protein-protein interactions and mention possible implications for novel pharmacological targets and strategies for treatment of diseases, e.g. neuroinflammatory diseases.
Subject(s)
Membrane Proteins/chemistry , Models, Theoretical , Protein Structure, Quaternary , Amino Acid Sequence , Membrane Proteins/genetics , Membrane Proteins/metabolism , Models, Molecular , Molecular Sequence Data , Protein MultimerizationABSTRACT
Common architecture of cytokine receptors and G-protein coupled receptors (GPCRs) may underlie pathological receptor heteromer formation and signaling. Here, we clarify how chemokines and cytokines can participate in pathogenic processes of Parkinson's disease, especially in dopaminergic neurons of substantia nigra. Possible common architecture of GPCRs and cytokine receptors suggests that they may act as molecular switches similar to the prototypical innate immune receptors: Toll-like receptors. Thus, pathological signaling (as well as trafficking and internalization) of receptors may be initiated by their incorrect dimerization depending on direct or indirect (via adaptor proteins) receptor-receptor interactions, leading to neuroinflammatory responses.
Subject(s)
Parkinson Disease/metabolism , Receptors, Cytokine/metabolism , Receptors, G-Protein-Coupled/physiology , Animals , Humans , Neurons/metabolism , Neurons/pathology , Parkinson Disease/complications , Parkinson Disease/pathologyABSTRACT
Receptor assemblies seem to play a key role in the integration and modulation of molecular signals of cell-cell communications. This may be confirmed by recent discoveries of the immunological synapse and cytokine networks which can be also treated within a sort of meta-system-neuroimmune molecular network. On the examples of receptor superfamilies expressed both in the neural and immune cells, our review paper aims to show some implications of receptor-receptor interactions for basal ganglia functions in health and disease.
