Conserved amino acids participate in the structure networks deputed to intramolecular communication in the lutropin receptor
| Autor: | Francesca Fanelli, David Puett, Moon Lee, Angelo Nicola Felline, Manish Patel, Krassimira Angelova |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Models
Molecular Protein Conformation G protein Biology Chorionic Gonadotropin Cellular and Molecular Neuroscience Protein structure Cyclic AMP Animals Humans Computer Simulation Amino Acids Molecular Biology G protein-coupled receptor Pharmacology chemistry.chemical_classification luteinizing hormone/choriogonadotropin receptor GPCRs Luteinizing Hormone Receptor Constitutive Activity Computational Modeling Molecular Dynamids Protein Structure Networks Cell Biology Receptors LH Amino acid HEK293 Cells Biochemistry chemistry Rhodopsin biology.protein Molecular Medicine Signal transduction Structural communication Signal Transduction |
| Popis: | The luteinizing hormone receptor (LHR) is a G protein-coupled receptor (GPCR) particularly susceptible to spontaneous pathogenic gain-of-function mutations. Protein structure network (PSN) analysis on wild-type LHR and two constitutively active mutants, combined with in vitro mutational analysis, served to identify key amino acids that are part of the regulatory network responsible for propagating communication between the extracellular and intracellular poles of the receptor. Highly conserved amino acids in the rhodopsin family GPCRs participate in the protein structural stability as network hubs in both the inactive and active states. Moreover, they behave as the most recurrent nodes in the communication paths between the extracellular and intracellular sides in both functional states with emphasis on the active one. In this respect, non-conservative loss-of-function mutations of these amino acids is expected to impair the most relevant way of communication between activating mutation sites or hormone-binding domain and G protein recognition regions. |
| Databáze: | OpenAIRE |
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