Conserved amino acids participate in the structure networks deputed to intramolecular communication in the lutropin receptor |
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Authors: | Krassimira Angelova Angelo Felline Moon Lee Manish Patel David Puett Francesca Fanelli |
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Institution: | (1) Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, USA;(2) Department of Chemistry, Dulbecco Telethon Institute, University of Modena and Reggio Emilia, 41125 Modena, Italy; |
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Abstract: | 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. |
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Keywords: | |
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