Structural insights into retinitis pigmentosa from unfolding simulations of rhodopsin mutants

摘要: Disease-causing missense mutations in membrane proteins, such as rhodopsin associated with the autosomal dominant form of retinitis pigmentosa (ADRP), are often linked to defects folding and/or trafficking. The mechanical unfolding wild-type was compared that 20 selected ADRP-linked mutants more or less defective and retinal binding. Rhodopsin fold is characterized by networks amino acids G-protein binding sites likely play a role stability function protein. distribution highly connected nodes network reflects existence diffuse intramolecular communication inside between 2 poles helix bundle, which makes pathogenic share similar phenotypes irrespective topological physicochemical differences them. Because this communication, marked ability impair hubs protein structure network. extent structural effect relates severity biochemical defect caused mutation. investigative strategy employed study apply all structurally known proteins particularly susceptible misassembly-causing mutations.