Localization and characterization of three different beta-adrenergic receptors expressed in Escherichia coli

Eur J Biochem. 1990 Jan 12;187(1):137-44. doi: 10.1111/j.1432-1033.1990.tb15287.x.

Abstract

After fusion with the N-proximal portion of the outer membrane protein LamB, three beta-adrenergic receptors, the human beta 1- and beta 2- and turkey beta 1-adrenergic receptor, were expressed in Escherichia coli with retention of their own specific pharmacological properties. Molecular characterization and localization of the three receptors in bacteria and comparison of the behaviour of each hybrid protein are reported. The bacteria were lysed and fractionated on a sucrose gradient. Saturable [125I]iodocyanopindolol binding activity was found associated mainly with the inner membrane fraction, suggesting that the receptor is correctly folded in this membrane. Binding activity was also found in the outer membrane fraction but varied according to the receptor type. Photoaffinity labeling experiments revealed that the receptors exhibit binding activity only after proteolytic removal of the LamB moiety from the fusion protein. The three hybrid proteins, detected in immunoblots by anti-peptide antibodies, were found mainly in the outer membrane fraction. Each of them exhibited different susceptibility to intrinsic bacterial proteolytic enzymes; sites of proteolytic cleavage were localized by the use of anti-peptide antibodies. The functional expression in E. coli of three beta-adrenergic receptors with similar structure but different amino acid sequences suggests that this expression system may be a general feature among similar receptors of the family of G-protein-coupled receptors. The level of expressed binding activity of a given receptor will be within the control of proteolytic degradation processes, depending on the primary sequence of the receptor. Constructions of new hybrid proteins, in combination with expression in protease mutants of E. coli, should help in controlling such processes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Membrane / metabolism
  • Cell Membrane / ultrastructure
  • Electrophoresis, Polyacrylamide Gel
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism
  • Gene Expression
  • Genes*
  • Humans
  • Immunoblotting
  • Iodocyanopindolol
  • Models, Structural
  • Molecular Sequence Data
  • Molecular Weight
  • Pindolol / analogs & derivatives
  • Pindolol / metabolism
  • Receptors, Adrenergic, beta / genetics
  • Receptors, Adrenergic, beta / isolation & purification
  • Receptors, Adrenergic, beta / metabolism*
  • Recombinant Fusion Proteins / isolation & purification
  • Recombinant Fusion Proteins / metabolism
  • Turkeys

Substances

  • Receptors, Adrenergic, beta
  • Recombinant Fusion Proteins
  • Iodocyanopindolol
  • Pindolol