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

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Daria A. Dmitrieva¹, Tatiana V. Kotova¹, Nadezda A. Safronova¹, Alexandra A. Sadova¹, Dmitrii E. Dashevskii¹, and Alexey V. Mishin^1,a*

¹Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Moscow Region, Russia

^* To whom correspondence should be addressed.

Received September 16, 2022; Revised October 5, 2022; Accepted October 14, 2022

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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.

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KEY WORDS: G protein-coupled receptors (GPCRs), genetic constructs, expression systems, protein complexes, methods for protein stabilization, purification and characterization of membrane proteins

DOI: 10.1134/S0006297923140110

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