Scholars@Duke

DeSiphering receptor core-induced and ligand-dependent conformational changes in arrestin via genetic encoded trimethylsilyl 1H-NMR probe.

Publication ,  Journal Article
Liu, Q; He, Q-T; Lyu, X; Yang, F; Zhu, Z-L; Xiao, P; Yang, Z; Zhang, F; Yang, Z-Y; Wang, X-Y; Sun, P; Wang, Q-W; Qu, C-X; Gong, Z; Lin, J-Y ...
Published in: Nat Commun
September 25, 2020
Published version (DOI) Link to item

Characterization of the dynamic conformational changes in membrane protein signaling complexes by nuclear magnetic resonance (NMR) spectroscopy remains challenging. Here we report the site-specific incorporation of 4-trimethylsilyl phenylalanine (TMSiPhe) into proteins, through genetic code expansion. Crystallographic analysis revealed structural changes that reshaped the TMSiPhe-specific amino-acyl tRNA synthetase active site to selectively accommodate the trimethylsilyl (TMSi) group. The unique up-field 1H-NMR chemical shift and the highly efficient incorporation of TMSiPhe enabled the characterization of multiple conformational states of a phospho-β2 adrenergic receptor/β-arrestin-1(β-arr1) membrane protein signaling complex, using only 5 μM protein and 20 min of spectrum accumulation time. We further showed that extracellular ligands induced conformational changes located in the polar core or ERK interaction site of β-arr1 via direct receptor transmembrane core interactions. These observations provided direct delineation and key mechanism insights that multiple receptor ligands were able to induce distinct functionally relevant conformational changes of arrestin.

Duke Scholars

Alem W Kahsai
Author Alem W Kahsai Medicine, Cardiology
Kunhong Xiao
Author Kunhong Xiao Medicine, Cardiology
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Published In

Nat Commun

DOI

10.1038/s41467-020-18433-5

EISSN

2041-1723

Publication Date

September 25, 2020

Volume

11

Issue

1

Start / End Page

4857

Location

England

Related Subject Headings

  • beta-Arrestin 1
  • Signal Transduction
  • Receptors, Adrenergic, beta-2
  • Proton Magnetic Resonance Spectroscopy
  • Protein Conformation
  • Protein Binding
  • Phenylalanine
  • Models, Molecular
  • Ligands
  • Humans
 

Citation

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Chicago
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MLA
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Liu, Q., He, Q.-T., Lyu, X., Yang, F., Zhu, Z.-L., Xiao, P., … Sun, J.-P. (2020). DeSiphering receptor core-induced and ligand-dependent conformational changes in arrestin via genetic encoded trimethylsilyl 1H-NMR probe. Nat Commun, 11(1), 4857. https://doi.org/10.1038/s41467-020-18433-5
Liu, Qi, Qing-Tao He, Xiaoxuan Lyu, Fan Yang, Zhong-Liang Zhu, Peng Xiao, Zhao Yang, et al. “DeSiphering receptor core-induced and ligand-dependent conformational changes in arrestin via genetic encoded trimethylsilyl 1H-NMR probe.” Nat Commun 11, no. 1 (September 25, 2020): 4857. https://doi.org/10.1038/s41467-020-18433-5.
Liu, Qi, et al. “DeSiphering receptor core-induced and ligand-dependent conformational changes in arrestin via genetic encoded trimethylsilyl 1H-NMR probe.” Nat Commun, vol. 11, no. 1, Sept. 2020, p. 4857. Pubmed, doi:10.1038/s41467-020-18433-5.
Liu Q, He Q-T, Lyu X, Yang F, Zhu Z-L, Xiao P, Yang Z, Zhang F, Yang Z-Y, Wang X-Y, Sun P, Wang Q-W, Qu C-X, Gong Z, Lin J-Y, Xu Z, Song S-L, Huang S-M, Guo S-C, Han M-J, Zhu K-K, Chen X, Kahsai AW, Xiao K-H, Kong W, Li F-H, Ruan K, Li Z-J, Yu X, Niu X-G, Jin C-W, Wang J, Sun J-P. DeSiphering receptor core-induced and ligand-dependent conformational changes in arrestin via genetic encoded trimethylsilyl 1H-NMR probe. Nat Commun. 2020 Sep 25;11(1):4857.

Published In

Nat Commun

DOI

10.1038/s41467-020-18433-5

EISSN

2041-1723

Publication Date

September 25, 2020

Volume

11

Issue

1

Start / End Page

4857

Location

England

Related Subject Headings

  • beta-Arrestin 1
  • Signal Transduction
  • Receptors, Adrenergic, beta-2
  • Proton Magnetic Resonance Spectroscopy
  • Protein Conformation
  • Protein Binding
  • Phenylalanine
  • Models, Molecular
  • Ligands
  • Humans