RESUMEN
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.
RESUMEN
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).
Asunto(s)
Organismos Acuáticos/metabolismo , Integrinas/química , Poríferos/metabolismo , Multimerización de Proteína , Receptores de Dopamina D2/química , Receptores de Dopamina D2/metabolismo , Secuencia de Aminoácidos , Animales , Encéfalo/metabolismo , Evolución Molecular , Humanos , Datos de Secuencia Molecular , Alineación de SecuenciaRESUMEN
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.
Asunto(s)
Encéfalo/fisiología , Evolución Molecular , Geodia/genética , Integrinas/genética , Receptores de Superficie Celular/genética , Animales , Humanos , Datos de Secuencia Molecular , Filogenia , Receptor de Colecistoquinina B/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Receptor del Glutamato Metabotropico 5 , Receptor de Serotonina 5-HT1A/genética , Receptor de Serotonina 5-HT1B/genética , Receptor de Serotonina 5-HT1D/genética , Receptores Adrenérgicos alfa 2/genética , Receptores de GABA-B/genética , Receptores de Glutamato Metabotrópico/genética , Homología de Secuencia de AminoácidoRESUMEN
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.
Asunto(s)
Inmunoglobulina G/química , Inmunoglobulina M/química , Modelos Químicos , Secuencia de Aminoácidos , Animales , Epítopos/química , Epítopos/inmunología , Humanos , Cadenas Pesadas de Inmunoglobulina/química , Cadenas Ligeras de Inmunoglobulina/química , Inflamación Neurogénica/inmunología , Inflamación Neurogénica/metabolismo , Neuroinmunomodulación/genética , Neuroinmunomodulación/inmunología , Dominios y Motivos de Interacción de Proteínas/inmunología , Multimerización de Proteína/inmunología , Receptores de GABA-B/química , Homología de Secuencia de AminoácidoRESUMEN
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.
Asunto(s)
Receptores de Neurotransmisores/química , Receptores Toll-Like/química , Secuencia de Aminoácidos , Animales , Humanos , Datos de Secuencia Molecular , Subunidades de Proteína/química , Subunidades de Proteína/genética , Proteínas Tirosina Quinasas Receptoras/química , Proteínas Tirosina Quinasas Receptoras/genética , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/genética , Receptores de GABA-A/química , Receptores de GABA-A/genética , Receptores de Neurotransmisores/genética , Transducción de Señal/fisiología , Receptores Toll-Like/genéticaRESUMEN
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.
Asunto(s)
Secuencias de Aminoácidos , Dominios y Motivos de Interacción de Proteínas/genética , Multimerización de Proteína , Receptores de GABA-B/química , Receptores de GABA-B/genética , Animales , Humanos , Modelos Moleculares , Datos de Secuencia Molecular , Unión Proteica , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Receptores de GABA-B/metabolismo , Alineación de SecuenciaRESUMEN
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.
Asunto(s)
Proteínas de la Membrana/química , Modelos Teóricos , Estructura Cuaternaria de Proteína , Secuencia de Aminoácidos , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Modelos Moleculares , Datos de Secuencia Molecular , Multimerización de ProteínaRESUMEN
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.
Asunto(s)
Enfermedad de Parkinson/metabolismo , Receptores de Citocinas/metabolismo , Receptores Acoplados a Proteínas G/fisiología , Animales , Humanos , Neuronas/metabolismo , Neuronas/patología , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/patologíaRESUMEN
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.
