title: Conformation of receptor-bound visual arrestin.
abstract: 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.
authors.affiliation: Jules Stein Eye Institute, Department of Ophthalmology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Miyeon
authors.initials: M
authors.lastname: Kim
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Vishnivetskiy
authors.forename: Ned
authors.initials: N
authors.lastname: Van Eps
authors.forename: Nathan S
authors.initials: NS
authors.lastname: Alexander
authors.forename: Whitney M
authors.initials: WM
authors.lastname: Cleghorn
authors.forename: Xuanzhi
authors.initials: X
authors.lastname: Zhan
authors.forename: Susan M
authors.initials: SM
authors.lastname: Hanson
authors.forename: Takefumi
authors.initials: T
authors.lastname: Morizumi
authors.forename: Oliver P
authors.initials: OP
authors.lastname: Ernst
authors.forename: Jens
authors.initials: J
authors.lastname: Meiler
authors.forename: Vsevolod V
authors.initials: VV
authors.lastname: Gurevich
authors.forename: Wayne L
authors.initials: WL
authors.lastname: Hubbell
mesh_terms: D019393:Arrestin / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004583:Electrons; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D055503:Protein Multimerization; D055550:Protein Stability; D017433:Protein Structure, Secondary; D012243:Rhodopsin / Q000378:metabolism*; D017384:Sequence Deletion; D012996:Solutions; D013194:Staining and Labeling; D013696:Temperature
chemical_list: D019393:Arrestin; D050505:Mutant Proteins; D012996:Solutions; D012243:Rhodopsin