Conformation of receptor-bound visual arrestin

• Published in: Proceedings of the National Academy of Sciences - PNAS 2012-11, Vol.109 (45), p.18407-18412
• Main Authors: Kim, Miyeon, Vishnivetskiy, Sergey A, Van Eps, Ned, Alexander, Nathan S, Cleghorn, Whitney M, Zhan, Xuanzhi, Hanson, Susan M, Morizumi, Takefumi, Ernst, Oliver P, Meiler, Jens, Gurevich, Vsevolod V, Hubbell, Wayne L
• Format: Article
• Language: English
• Subjects: Arrestin - chemistry; Arrestin - metabolism; Binding sites; Biochemistry; Biological Sciences; Crystal structure; Crystallography, X-Ray; Crystals; Electrons; Fingers; G-proteins; Models, Molecular; Molecules; Monomers; Mutagenesis; Mutant Proteins - chemistry; Mutant Proteins - metabolism; Phosphorylation; Physiological regulation; Protein Binding; Protein Multimerization; Protein Stability; Protein Structure, Secondary; Proteins; Receptors; rhodopsin; Rhodopsin - metabolism; Sequence Deletion; Solutions; Spin labels; Staining and Labeling; Temperature
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1216304109

Arrestin-1 (visual arrestin) binds to light-activated phosphorylated rhodopsin (P-Rh*) to terminate G-protein signaling. To map conformational changes upon binding to the receptor, pairs of spin labels were introduced in arrestin-1 and double electron–electron resonance was used to monitor interspin distance changes upon P-Rh* binding. The results indicate that the relative position of the N and C domains remains largely unchanged, contrary to expectations of a “clam-shell” model. A loop implicated in P-Rh* binding that connects β-strands V and VI (the “finger loop,” residues 67–79) moves toward the expected location of P-Rh* in the complex, but does not assume a fully extended conformation. A striking and unexpected movement of a loop containing residue 139 away from the adjacent finger loop is observed, which appears to facilitate P-Rh* binding. This change is accompanied by smaller movements of distal loops containing residues 157 and 344 at the tips of the N and C domains, which correspond to “plastic” regions of arrestin-1 that have distinct conformations in monomers of the crystal tetramer. Remarkably, the loops containing residues 139, 157, and 344 appear to have high flexibility in both free arrestin-1 and the P-Rh*complex.