Protein Design Strategies for the Structural-Functional Studies of G Protein-Coupled Receptors

Biochemistry (Mosc). 2023 Jan;88(Suppl 1):S192-S226. doi: 10.1134/S0006297923140110.

Abstract

G protein-coupled receptors (GPCRs) are an important family of membrane proteins responsible for many physiological functions in human body. High resolution GPCR structures are required to understand their molecular mechanisms and perform rational drug design, as GPCRs play a crucial role in a variety of diseases. That is difficult to obtain for the wild-type proteins because of their low stability. In this review, we discuss how this problem can be solved by using protein design strategies developed to obtain homogeneous stabilized GPCR samples for crystallization and cryoelectron microscopy.

Keywords: G protein-coupled receptors (GPCRs); expression systems; genetic constructs; methods for protein stabilization; protein complexes; purification and characterization of membrane proteins.

Publication types

  • Review

MeSH terms

  • Cryoelectron Microscopy
  • Crystallization
  • Humans
  • Membrane Proteins*
  • Models, Molecular
  • Receptors, G-Protein-Coupled* / chemistry
  • Receptors, G-Protein-Coupled* / metabolism

Substances

  • Receptors, G-Protein-Coupled
  • Membrane Proteins