RESUMEN
Class F G protein-coupled receptors are characterized by a large extracellular domain (ECD) in addition to the common transmembrane domain (TMD) with seven α-helixes. For smoothened receptor (SMO), structural studies revealed dissected ECD and TMD, and their integrated assemblies. However, distinct assemblies were reported under different circumstances. Using an unbiased approach based on four series of cross-conjugated bitopic ligands, we explore the relationship between the active status and receptor assembly. Different activity dependency on the linker length for these bitopic ligands corroborates the various occurrences of SMO assembly. These results reveal a rigid "near" assembly for active SMO, which is in contrast to previous results. Conversely, inactive SMO adopts a free ECD, which would be remotely captured at "far" assembly by cholesterol. Altogether, we propose a mechanism of cholesterol flow-caused SMO activation involving an erection of ECD from far to near assembly.
Asunto(s)
Hidroxicolesteroles/metabolismo , Receptor Smoothened/metabolismo , Anilidas/síntesis química , Anilidas/metabolismo , Animales , Sitios de Unión , Células HEK293 , Humanos , Hidroxicolesteroles/síntesis química , Ligandos , Ratones , Células 3T3 NIH , Polietilenglicoles/síntesis química , Polietilenglicoles/metabolismo , Dominios Proteicos , Piridinas/síntesis química , Piridinas/metabolismo , Receptor Smoothened/agonistas , Receptor Smoothened/antagonistas & inhibidores , Receptor Smoothened/químicaRESUMEN
Phosphorus-doped activated carbon is reported for the first time as a highly selective catalyst for n-hexane dehydroaromatization to benzene and hydrogen with 100% n-hexane conversion and 97% benzene selectivity. The weak/medium-strength acidic centres composed of (CO)(C)-P(O)(OH) units on the catalyst surface would be the catalytic active sites. This work provides a new alternative in the preparation of metal-free catalysts for the highly selective functionalization of C-H bonds of n-alkanes.
