TY  - JOUR
AU  - Cutsail, George
AU  - Schott-Verdugo, Stephan
AU  - Müller, Lena
AU  - DeBeer, Serena
AU  - Groth, Georg
AU  - Gohlke, Holger
TI  - Spectroscopic and QM/MM studies of the Cu(I) binding site of the plant ethylene receptor ETR1
JO  - Biophysical journal
VL  - 121
IS  - 20
SN  - 0006-3495
CY  - Bethesda, Md.
PB  - Soc.
M1  - FZJ-2022-03395
SP  - 3862-3873
PY  - 2022
AB  - Herein, we present, to our knowledge, the first spectroscopic characterization of the Cu(I) active site of the plant ethylene receptor ETR1. The x-ray absorption (XAS) and extended x-ray absorption fine structure (EXAFS) spectroscopies presented here establish that ETR1 has a low-coordinate Cu(I) site. The EXAFS resolves a mixed first coordination sphere of N/O and S scatterers at distances consistent with potential histidine and cysteine residues. This finding agrees with the coordination of residues C65 and H69 to the Cu(I) site, which are critical for ethylene activity and well conserved. Furthermore, the Cu K-edge XAS and EXAFS of ETR1 exhibit spectroscopic changes upon addition of ethylene that are attributed to modifications in the Cu(I) coordination environment, suggestive of ethylene binding. Results from umbrella sampling simulations of the proposed ethylene binding helix of ETR1 at a mixed quantum mechanics/molecular mechanics level agree with the EXAFS fit distance changes upon ethylene binding, particularly in the increase of the distance between H69 and Cu(I), and yield binding energetics comparable with experimental dissociation constants. The observed changes in the copper coordination environment might be the triggering signal for the transmission of the ethylene response.
LB  - PUB:(DE-HGF)16
C6  - 36086818
UR  - <Go to ISI:>//WOS:000928435100011
DO  - DOI:10.1016/j.bpj.2022.09.007
UR  - https://juser.fz-juelich.de/record/909765
ER  -