Mutation of a highly conserved aspartic acid in the β2 adrenergic receptor: Constitutive activation, structural instability, and conformational rearrangement of transmembrane segment 6

Molecular Pharmacology

Volumn 56, Issue 1, 1999, Pages 175-184

  Rasmussen, SØren G F ^a   Jensen, Anne D ^a   Liapakis, George ^b   Ghanouni, Pejman ^a   Javitch, Jonathan A ^b   Gether, Ulrik ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b Columbia Univ Coll Phys Surgs ^*  (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ASPARTIC ACID; BETA 2 ADRENERGIC RECEPTOR; ISOPRENALINE; PINDOLOL;

ANIMAL CELL; ARTICLE; CONFORMATIONAL TRANSITION; LIGAND BINDING; MOLECULAR INTERACTION; MOLECULAR STABILITY; NONHUMAN; PRIORITY JOURNAL; PROTON TRANSPORT; RECEPTOR BINDING; RECEPTOR DENSITY; RECEPTOR INTRINSIC ACTIVITY; SITE DIRECTED MUTAGENESIS;

EID: 0033061256     PISSN: 0026895X     EISSN: None     Source Type: Journal    
DOI: 10.1124/mol.56.1.175     Document Type: Article

References (39)

1. Arnis S, Fahmy K, Hofmann KP and Sakmar TP (1994) A conserved carboxylic acid group mediates light-dependent proton uptake and signaling by rhodopsin. J Biol Chem 269:23879-23881.
2. Baldwin JM, Schertler GF and Unger VM (1997) An alpha-carbon template for the transmembrane helices in the rhodopsin family of G-protein-coupled receptors. J Mol Biol 272:144-164.
3. Ballesteros J, Kitanovic S, Guarnieri F, Davies P, Fromme BJ, Konvicka K, Chi L, Millar RP, Davidson JS, Weinstein H and Sealfon SC (1998) Functional microdomains in G-protein-coupled receptors. The conserved arginine-cage motif in the gonadotropin-releasing hormone receptor. J Biol Chem 273:10445-10453.
4. Ballesteros JA and Weinstein H (1995) Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein coupled receptors. Methods Neurosci 25:366-428.
5. Chidiac P, Hebert TE, Valiquette M, Dennis M and Bouvier M (1994) Inverse agonist activity of beta-adrenergic antagonists. Mol Pharmacol 45:490-499.
6. Cohen GB, Yang T, Robinson PR and Oprian DD (1993) Constitutive activation of opsin: Influence of charge at position 134 and size at position 296. Biochemistry 32:6111-6115.
7. Farrens DL, Altenbach C, Yang K, Hubbell WL and Khorana HG (1996) Requirement of rigid-body motion of transmembrane helices for light activation of rhodopsin. Science (Wash DC) 274:768-770.
8. Fraser CM, Chung FZ, Wang CD and Venter JC (1988) Site-directed mutagenesis of human beta-adrenergic receptors: Substitution of aspartic acid-130 by asparagine produces a receptor with high-affinity agonist binding that is uncoupled from adenylate cyclase. Proc Natl Acad Sci USA 85:5478-5482.
9. Gether U, Ballesteros JA, Seifert R, Sanders-Bush E, Weinstein H and Kobilka BK (1997a) Structural instability of a constitutively active G protein-coupled receptor. Agonist-independent activation due to conformational flexibility. J Biol Chem 272:2587-2590.
10. Gether U and Kobilka BK (1998) G protein-coupled receptors. II. Mechanism of agonist activation. J Biol Chem 273:17979-17982.
11. Gether U, Lin S, Ghanouni P, Ballesteros JA, Weinstein H and Kobilka BK (1997b) Agonists induce conformational changes in transmembrane domains III and VI of the beta2 adrenoceptor. EMBO J 16:6737-6747.
12. Gether U, Lin S and Kobilka BK (1995) Fluorescent labeling of purified beta2-adrenergic receptor: Evidence for ligand-specific conformational changes. J Biol Chem 270:28268-28275.
13. Guan XM, Kobilka TS and Kobilka BK (1992) Enhancement of membrane insertion and function in a type IIIb membrane protein following introduction of a cleaveable signal peptide. J Biol Chem 267:21995-21998.
14. Han M, Lou J, Nakanishi K, Sakmar TP and Smith SO (1997) Partial agonist activity of 11-cis-retinal in rhodopsin mutants. J Biol Chem 272:23081-23085.
15. Hjorth SA, Orskov C and Schwartz TW (1998) Constitutive activity of glucagon receptor mutants. Mol Endocrinol 12:78-86.
16. Javitch JA, Fu D, Chen J and Karlin A (1995) Mapping the binding-site crevice of the dopamine D2 receptor by the substituted-cysteine accessibility method. Neuron 14:825-831.
17. Javitch JA, Fu D, Liapakis G and Chen J (1997) Constitutive activation of the beta2 adrenergic receptor alters the orientation of its sixth membrane-spanning segment. J Biol Chem 272:18546-18549.
18. Javitch JA, Li X, Kaback J and Karlin A (1994) A cysteine residue in the third membrane-spanning segment of the human D2 dopamine receptor is exposed in the binding-site crevice. Proc Natl Acad Sci USA 91:10355-10359.
19. Ji TH, Grossmann M and Ji I (1998) G protein-coupled receptors. I. Diversity of receptor-ligand interactions. J Biol Chem 273:17299-17302.
20. Johansen TE, Scholler MS, Tolstoy S and Schwartz TW (1990) Biosynthesis of peptide precursors and protease inhibitors using new constitutive and inducible eukaryotic expression vectors. FEBS Lett 267:289-294.
21. Kim JM, Altenbach C, Thurmond RL, Khorana HG and Hubbell WL (1997) Structure and function in rhodopsin: Rhodopsin mutants with a neutral amino acid at E134 have a partially activated conformation in the dark state. Proc Natl Acad Sci USA 94:14273-14278.
22. Kjelsberg MA, Cotecchia S, Ostrowski J, Caron MG and Lefkowitz RJ (1992) Constitutive activation of the alpha 1B-adrenergic receptor by all amino acid substitutions at a single site. Evidence for a region which constrains receptor activation. J Biol Chem 267:1430-1433.
23. Lu ZL, Curtis CA, Jones PG, Pavia J and Hulme EC (1997) The role of the aspartate-arginine-tyrosine triad in the m1 muscarinic receptor: Mutations of aspartate 122 and tyrosine 124 decrease receptor expression but do not abolish signaling. Mol Pharmacol 51:234-241.
24. Min KC, Zvyaga TA, Cypess AM and Sakmar TP (1993) Characterization of mutant rhodopsins responsible for autosomal dominant retinitis pigmentosa. Mutations on the cytoplasmic surface affect transducin activation. J Biol Chem 268:9400-9404.
25. Porter JE, Hwa J and Perez DM (1996) Activation of the alpha1b-adrenergic receptor is initiated by disruption of an interhelical salt bridge constraint. J Biol Chem 271:28318-28323.
26. Probst WC, Snyder LA, Schuster DI, Brosius J and Sealfon SC (1992) Sequence alignment of the G-protein coupled receptor superfamily. DNA Cell Biol 11:1-20.
27. Roberts DD, Lewis SD, Ballou DP, Olson ST and Shafer JA (1986) Reactivity of small thiolate anions and cysteine-25 in papain toward methyl methanethiosulfonate. Biochemistry 25:5595-5601.
28. Rosenthal W, Antaramian A, Gilbert S and Birnbaumer M (1993) Nephrogenic diabetes insipidus. A V2 vasopressin receptor unable to stimulate adenylyl cyclase. J Biol Chem 268:13030-13033.
29. Salomon Y, Londos C and Rodbell M (1974) A highly sensitive adenylate cyclase assay. Anal Biochem 58:541-548.
30. Samama P, Cotecchia S, Costa T and Lefkowitz RJ (1993) A mutation-induced activated state of the beta2-adrenergic receptor: Extending the ternary complex model. J Biol Chem 268:4625-4636.
31. Scheer A, Fanelli F, Costa T, De Benedetti PG and Cotecchia S (1996) Constitutively active mutants of the alpha 1B-adrenergic receptor: Role of highly conserved polar amino acids in receptor activation. EMBO J 15:3566-3578.
32. Scheer A, Fanelli F, Costa T, De Benedetti PG and Cotecchia S (1997) The activation process of the alpha 1B-adrenergic receptor: Potential role of protonation and hydrophobicity of a highly conserved aspartate. Proc Natl Acad Sci USA 94:808-813.
33. Sheikh SP, Zvyaga TA, Lichtarge O, Sakmar TP and Bourne HR (1996) Rhodopsin activation blocked by metal-ion-binding sites linking transmembrane helices C and F. Nature (Lond) 383:347-350.
34. Schertler GF, Villa C and Henderson R (1993) Projection structure of rhodopsin. Nature (Lond) 362:770-772.
35. Stauffer DA and Karlin A (1994) Electrostatic potential of the acetylcholine binding sites in the nicotinic receptor probed by reactions of binding-site cysteines with charged methanethiosulfonates. Biochemistry 33:6840-6849.
36. Strader CD, Fong TM, Tota MR, Underwood D and Dixon RAF (1994) Structure and function of G protein-coupled receptors. Annu Rev Biochem 63:101-132.
37. Suryanarayana S and Kobilka BK (1991) Construction and expression of chimeric receptors to understand the structure-function relationships in adrenergic receptors. Methods (Orlando) 3:193-204.
38. Unger VM, Hargrave PA, Baldwin JM and Schertler GF (1997) Arrangement of rhodopsin transmembrane alpha-helices. Nature (Lond) 389:203-206.
39. Yu H, Kono M, McKee TD and Oprian DD (1995) A general method for mapping tertiary contacts between amino acid residues in membrane-embedded proteins. Biochemistry 34:14963-14969.