Differences between G-Protein-Stabilized Agonist-GPCR Complexes and their Nanobody-Stabilized Equivalents

Saleh N, Ibrahim P, Clark T (2017)


Publication Status: Published

Publication Type: Journal article

Publication year: 2017

Journal

Publisher: WILEY-V C H VERLAG GMBH

Book Volume: 56

Pages Range: 9008-9012

Journal Issue: 31

DOI: 10.1002/anie.201702468

Abstract

Protein nanobodies have been used successfully as surrogates for unstable G-proteins in order to crystallize G-protein-coupled receptors (GPCRs) in their active states. We used molecular dynamics (MD) simulations, including meta-dynamics enhanced sampling, to investigate the similarities and differences between GPCR-agonist ternary complexes with the alpha-subunits of the appropriate G-proteins and those with the protein nanobodies (intracellular binding partners, IBPs) used for crystallization. In two of the three receptors considered, the agonist-binding mode differs significantly between the two alternative ternary complexes. The ternary-complex model of GPCR activation entails enhancement of ligand binding by bound IBPs: Our results show that IBP-specific changes can alter the agonist binding modes and thus also the criteria for designing GPCR agonists.

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How to cite

APA:

Saleh, N., Ibrahim, P., & Clark, T. (2017). Differences between G-Protein-Stabilized Agonist-GPCR Complexes and their Nanobody-Stabilized Equivalents. Angewandte Chemie International Edition, 56(31), 9008-9012. https://dx.doi.org/10.1002/anie.201702468

MLA:

Saleh, Noureldin, Passainte Ibrahim, and Timothy Clark. "Differences between G-Protein-Stabilized Agonist-GPCR Complexes and their Nanobody-Stabilized Equivalents." Angewandte Chemie International Edition 56.31 (2017): 9008-9012.

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