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Structures of the archaerhodopsin-3 transporter reveal that disordering of internal water networks underpins receptor sensitization

DOI: 10.1038/s41467-020-20596-0 DOI Help

Authors: Juan F. Bada Juarez (Oxford University) , Peter J. Judge (Oxford University) , Suliman Adam (Hebrew University of Jerusalem) , Danny Axford (Diamond Light Source) , Javier Vinals (Oxford University) , James Birch (Diamond Light Source; Research Complex at Harwell) , Tristan O. C. Kwan (Research Complex at Harwell; National Physical Laboratory) , Kin Kuan Hoi (Oxford University) , Hsin-Yung Yen (OMass Therapeutics) , Anthony Vial (INSERM, CNRS, University of Montpellier) , Pierre-Emmanuel Milhiet (INSERM, CNRS, University of Montpellier) , Carol V. Robinson (Oxford University) , Igor Schapiro (Hebrew University of Jerusalem) , Isabel Moraes (Research Complex at Harwell; National Physical Laboratory) , Anthony Watts (Oxford University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 12

State: Published (Approved)
Published: January 2021
Diamond Proposal Number(s): 19152 , 11386 , 15222

Open Access Open Access

Abstract: Many transmembrane receptors have a desensitized state, in which they are unable to respond to external stimuli. The family of microbial rhodopsin proteins includes one such group of receptors, whose inactive or dark-adapted (DA) state is established in the prolonged absence of light. Here, we present high-resolution crystal structures of the ground (light-adapted) and DA states of Archaerhodopsin-3 (AR3), solved to 1.1 Å and 1.3 Å resolution respectively. We observe significant differences between the two states in the dynamics of water molecules that are coupled via H-bonds to the retinal Schiff Base. Supporting QM/MM calculations reveal how the DA state permits a thermodynamic equilibrium between retinal isomers to be established, and how this same change is prevented in the ground state in the absence of light. We suggest that the different arrangement of internal water networks in AR3 is responsible for the faster photocycle kinetics compared to homologs.

Journal Keywords: Computational biophysics; Membrane biophysics; Membrane proteins; X-ray crystallography

Subject Areas: Biology and Bio-materials

Diamond Offline Facilities: Membrane Protein Laboratory (MPL)
Instruments: B23-Circular Dichroism , I24-Microfocus Macromolecular Crystallography

Added On: 28/01/2021 08:49


Discipline Tags:

Biotechnology Health & Wellbeing Biochemistry Neurology Chemistry Structural biology Engineering & Technology Biophysics Life Sciences & Biotech

Technical Tags:

Diffraction Spectroscopy Macromolecular Crystallography (MX) Circular Dichroism (CD)