scholarly journals The Structural Basis of Peptide Binding at Class A G Protein-Coupled Receptors

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 210
Author(s):  
Oanh Vu ◽  
Brian Joseph Bender ◽  
Lisa Pankewitz ◽  
Daniel Huster ◽  
Annette G. Beck-Sickinger ◽  
...  

G protein-coupled receptors (GPCRs) represent the largest membrane protein family and a significant target class for therapeutics. Receptors from GPCRs’ largest class, class A, influence virtually every aspect of human physiology. About 45% of the members of this family endogenously bind flexible peptides or peptides segments within larger protein ligands. While many of these peptides have been structurally characterized in their solution state, the few studies of peptides in their receptor-bound state suggest that these peptides interact with a shared set of residues and undergo significant conformational changes. For the purpose of understanding binding dynamics and the development of peptidomimetic drug compounds, further studies should investigate the peptide ligands that are complexed to their cognate receptor.

PLoS ONE ◽  
2015 ◽  
Vol 10 (9) ◽  
pp. e0138463 ◽  
Author(s):  
Adam L. Martin ◽  
Michael A. Steurer ◽  
Robert S. Aronstam

2021 ◽  
Author(s):  
May Meltzer ◽  
Zvagelsky Tatiana ◽  
Niv Papo ◽  
Stanislav Engel

Abstract The immense potential of G protein-coupled receptors (GPCRs) as targets for drug discovery is not fully realized due to the enormous difficulties associated with structure elucidation of these profoundly unstable membrane proteins. The existing methods of GPCR stability-engineering are cumbersome and low-throughput; in addition, the scope of GPCRs that could benefit from these techniques is limited. Here, we presented a yeast-based screening platform for a single-step isolation of GRCR variants stable in the presence of short-chain detergents, a feature essential for their successful crystallization using vapor diffusion method. The detergent-resistant cell wall of yeast provides a unique compartmentalization opportunity to physically link the receptor phenotype to its encoding DNA, and thus enable discovery of stable GPCR variants with unprecedent efficiency. The scope of mutations identified by the method offers important insights into the structural basis of GPCR stability, questioning the inherent instability of the GPCR scaffold, and revealing the potential role of the C-terminus in receptor stabilization.


FEBS Letters ◽  
2019 ◽  
Vol 593 (10) ◽  
pp. 1113-1121 ◽  
Author(s):  
Wanhui Hu ◽  
Huixia Wang ◽  
Yaguang Hou ◽  
Yimei Hao ◽  
Dongsheng Liu

2018 ◽  
Vol 130 (12) ◽  
pp. 3102-3107 ◽  
Author(s):  
Balaji Selvam ◽  
Zahra Shamsi ◽  
Diwakar Shukla

2019 ◽  
Vol 1861 (12) ◽  
pp. 183051 ◽  
Author(s):  
Daria N. Shalaeva ◽  
Dmitry A. Cherepanov ◽  
Michael Y. Galperin ◽  
Gert Vriend ◽  
Armen Y. Mulkidjanian

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