Visual arrestin activity may be regulated by self-association

被引:64
作者
Schubert, C
Hirsch, JA
Gurevich, VV
Engelman, DM
Sigler, PB
Fleming, KG
机构
[1] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA
[2] Yale Univ, Howard Hughes Med Inst, New Haven, CT 06520 USA
[3] Sun Hlth Res Inst, Ralph & Muriel Roberts Lab Vis Sci, Sun City, AZ 85372 USA
关键词
D O I
10.1074/jbc.274.30.21186
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Visual arrestin is the protein responsible for rapid quenching of G-protein-coupled receptor signaling. Arrestin exists as a latent inhibitor which must be 'activated' upon contact with a phosphorylated receptor. X-ray crystal structures of visual arrestin exhibit a tetrameric arrangement wherein an asymmetric dimer with an extensive interface between conformationally different subunits is related to a second asymmetric dimer by a local two-fold rotation axis. To test the biological relevance of this molecular organization in solution, we carried out a sedimentation, equilibrium analysis of arrestin at both crystallographic and physiological protein concentrations.. While the tetrameric form can exist at the high concentrations used in crystallography experiments, we find that arrestin participates in a monomer/dimer equilibrium at concentrations more likely to be physiologically relevant. Solution interaction analysis of a proteolytically modified, constitutively active form of arrestin shows diminished dimerization. We propose that self-association of arrestin may provide a mechanism for regulation of arrestin activity by (i) ensuring an adequate supply for rapid quenching of the visual signal and. (ii) limiting the availability of active monomeric species, thereby preventing inappropriate signal termination.
引用
收藏
页码:21186 / 21190
页数:5
相关论文
共 22 条
[1]   Slow dimer dissociation of the TATA binding protein dictates the kinetics of DNA binding [J].
Coleman, RA ;
Pugh, BF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (14) :7221-7226
[2]   DIMERIZATION OF THE TATA-BINDING PROTEIN [J].
COLEMAN, RA ;
TAGGART, AKP ;
BENJAMIN, LR ;
PUGH, BF .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (23) :13842-13849
[3]   X-ray crystal structure of arrestin from bovine rod outer segments [J].
Granzin, J ;
Wilden, U ;
Choe, HW ;
Labahn, J ;
Krafft, B ;
Büldt, G .
NATURE, 1998, 391 (6670) :918-921
[4]   Arrestin with a single amino acid substitution quenches light-activated rhodopsin in a phosphorylation-independent fashion [J].
GrayKeller, MP ;
Detwiler, PB ;
Benovic, JL ;
Gurevich, VV .
BIOCHEMISTRY, 1997, 36 (23) :7058-7063
[5]  
GUREVICH VV, 1993, J BIOL CHEM, V268, P11628
[6]   Agonist-receptor-arrestin, an alternative ternary complex with high agonist affinity [J].
Gurevich, VV ;
PalsRylaarsdam, R ;
Benovic, JL ;
Hosey, MM ;
Onorato, JJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (46) :28849-28852
[7]  
GUREVICH VV, 1994, J BIOL CHEM, V269, P8721
[8]   ARRESTIN INTERACTIONS WITH G-PROTEIN-COUPLED RECEPTORS - DIRECT BINDING-STUDIES OF WILD-TYPE AND MUTANT ARRESTINS WITH RHODOPSIN, BETA(2)-ADRENERGIC, AND M2-MUSCARINIC CHOLINERGIC RECEPTORS [J].
GUREVICH, VV ;
DION, SB ;
ONORATO, JJ ;
PTASIENSKI, J ;
KIM, CM ;
STERNEMARR, R ;
HOSEY, MM ;
BENOVIC, JL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (02) :720-731
[9]   Mechanism of phosphorylation-recognition by visual arrestin and the transition of arrestin into a high affinity binding state [J].
Gurevich, VV ;
Benovic, JL .
MOLECULAR PHARMACOLOGY, 1997, 51 (01) :161-169
[10]   The selectivity of visual arrestin for light-activated phosphorhodopsin is controlled by multiple nonredundant mechanisms [J].
Gurevich, VV .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (25) :15501-15506