TY - JOUR
T1 - Structural characterization of receptor–receptor interactions in the allosteric modulation of G protein-coupled receptor (Gpcr) dimers
AU - Lazim, Raudah
AU - Suh, Donghyuk
AU - Lee, Jai Woo
AU - Vu, Thi Ngoc Lan
AU - Yoon, Sanghee
AU - Choi, Sun
N1 - Funding Information:
Funding: This work was supported by the Mid-career Researcher Program (NRF-2020R1A2C2101636), Medical Research Center (MRC) grant (NRF-2018R1A5A2025286), and Bio & Medical Technology Development Program (NRF-2019M3E5D4065251) funded by the Ministry of Science and ICT (MSIT) and the Ministry of Health and Welfare (MOHW) through the National Research Foundation of Korea (NRF). This work was also supported by the Ewha Womans University Research Grant of 2021 (to S.C.) and by the RP-Grant 2020 of Ewha Womans University (to R.L.).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/3/2
Y1 - 2021/3/2
N2 - G protein-coupled receptor (GPCR) oligomerization, while contentious, continues to at-tract the attention of researchers. Numerous experimental investigations have validated the presence of GPCR dimers, and the relevance of dimerization in the effectuation of physiological functions intensifies the attractiveness of this concept as a potential therapeutic target. GPCRs, as a single entity, have been the main source of scrutiny for drug design objectives for multiple diseases such as cancer, inflammation, cardiac, and respiratory diseases. The existence of dimers broadens the research scope of GPCR functions, revealing new signaling pathways that can be targeted for disease pathogenesis that have not previously been reported when GPCRs were only viewed in their monomeric form. This review will highlight several aspects of GPCR dimerization, which include a summary of the structural elucidation of the allosteric modulation of class C GPCR activation offered through recent solutions to the three-dimensional, full-length structures of metabotropic glutamate receptor and γ-aminobutyric acid B receptor as well as the role of dimerization in the modification of GPCR function and allostery. With the growing influence of computational methods in the study of GPCRs, we will also be reviewing recent computational tools that have been utilized to map protein–protein interactions (PPI).
AB - G protein-coupled receptor (GPCR) oligomerization, while contentious, continues to at-tract the attention of researchers. Numerous experimental investigations have validated the presence of GPCR dimers, and the relevance of dimerization in the effectuation of physiological functions intensifies the attractiveness of this concept as a potential therapeutic target. GPCRs, as a single entity, have been the main source of scrutiny for drug design objectives for multiple diseases such as cancer, inflammation, cardiac, and respiratory diseases. The existence of dimers broadens the research scope of GPCR functions, revealing new signaling pathways that can be targeted for disease pathogenesis that have not previously been reported when GPCRs were only viewed in their monomeric form. This review will highlight several aspects of GPCR dimerization, which include a summary of the structural elucidation of the allosteric modulation of class C GPCR activation offered through recent solutions to the three-dimensional, full-length structures of metabotropic glutamate receptor and γ-aminobutyric acid B receptor as well as the role of dimerization in the modification of GPCR function and allostery. With the growing influence of computational methods in the study of GPCRs, we will also be reviewing recent computational tools that have been utilized to map protein–protein interactions (PPI).
KW - Allosteric modulation
KW - Dimerization
KW - G protein-coupled receptor (GPCR)
KW - PPI prediction
KW - Peptide design
KW - Protein dy-namics
KW - Protein dynamics
KW - Receptor–receptor interaction
UR - http://www.scopus.com/inward/record.url?scp=85102766410&partnerID=8YFLogxK
U2 - 10.3390/ijms22063241
DO - 10.3390/ijms22063241
M3 - Review article
C2 - 33810175
AN - SCOPUS:85102766410
SN - 1661-6596
VL - 22
SP - 1
EP - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 6
M1 - 3241
ER -