Papers by Ana-nicoleta Bondar
PLOS ONE, 2018
Channelrhodopsins are light-sensitive ion channels whose reaction cycles involve conformation-cou... more Channelrhodopsins are light-sensitive ion channels whose reaction cycles involve conformation-coupled transfer of protons. Understanding how channelrhodopsins work is important for applications in optogenetics, where light activation of these proteins triggers changes in the transmembrane potential across excitable membranes. A fundamental open question is how the protein environment ensures that unproductive proton transfer from the retinal Schiff base to the nearby carboxylate counterion is avoided in the resting state of the channel. To address this question, we performed combined quantum mechanical/molecular mechanical proton transfer calculations with explicit treatment of the surrounding lipid membrane. The free energy profiles computed for proton transfer to the counterion, either via a direct jump or mediated by a water molecule, demonstrate that, when retinal is all-trans, water and protein electrostatic interactions largely favour the protonated retinal Schiff base state. We identified a conserved lysine group as an essential structural element for the proton transfer energetics in channelrhodopsins.
Physical chemistry chemical physics : PCCP, Jan 23, 2017
Microbial rhodopsins are well known as versatile and ubiquitous light-driven ion transporters and... more Microbial rhodopsins are well known as versatile and ubiquitous light-driven ion transporters and photosensors. While the proton transport mechanism has been studied in great detail, much less is known about various modes of anion transport. Until recently, only two main groups of light-driven anion pumps were known, archaeal halorhodopsins (HRs) and bacterial chloride pumps (known as ClRs or NTQs). Last year, another group of cyanobacterial anion pumps with a very distinct primary structure was reported. Here, we studied the chloride-transporting photocycle of a representative of this new group, Mastigocladopsis repens rhodopsin (MastR), using time-resolved spectroscopy in the infrared and visible ranges and site-directed mutagenesis. We found that, in accordance with its unique amino acid sequence containing many polar residues in the transmembrane region of the protein, its photocycle features a number of unusual molecular events not known for other anion-pumping rhodopsins. It a...
Journal of Computational Chemistry, 2017
Biochimica et Biophysica Acta (BBA) - Bioenergetics, 2015
Microbial rhodopsins are a versatile family of photoactive retinal-binding membrane proteins whic... more Microbial rhodopsins are a versatile family of photoactive retinal-binding membrane proteins which are widespread geographically and taxonomically. One of the main functions of microbial rhodopsins is outward-directed light-driven proton transport across the plasma membrane, which can provide sources of energy alternative to respiration and chlorophyll photosynthesis. Proton-pumping rhodopsins are found in Archaea (Halobacteria), multiple groups of Bacteria, numerous fungi, and some microscopic algae. This work describes a new group of efficient proteobacterial retinal-binding light-driven proton pumps which lack the carboxylic proton donor on helix C (most often replaced by Gly) but possess a unique His residue on helix B. The typical representative of the group (from Pseudomonas putida) was characterized spectroscopically and through site-directed mutagenesis, which suggested that the unique histidine at position 37 likely forms a proton-donating complex involving water molecules compensating for the loss of the carboxylic proton donor.
Biochimica et biophysica acta, 2014
Translocation of negatively charged ions across cell membranes by ion pumps raises the question a... more Translocation of negatively charged ions across cell membranes by ion pumps raises the question as to how protein interactions control the location and dynamics of the ion. Here we address this question by performing extensive molecular dynamics simulations of wild type and mutant halorhodopsin, a seven-helical transmembrane protein that translocates chloride ions upon light absorption. We find that inter-helical hydrogen bonds mediated by a key arginine group largely govern the dynamics of the protein and water groups coordinating the chloride ion.
Biophysical Journal, 2010
The light-induced isomerization of the retinal from 11-cis to all-trans triggers changes in the c... more The light-induced isomerization of the retinal from 11-cis to all-trans triggers changes in the conformation of visual rhodopsins that lead to the formation of the activated state, which is ready to interact with the G protein. To begin to understand how changes in the structure and dynamics of the retinal are transmitted to the protein, we performed molecular dynamics simulations of squid rhodopsin with 11-cis and all-trans retinal, and with two different force fields for describing the retinal molecule. The results indicate that structural rearrangements in the binding pocket, albeit small, propagate toward the cytoplasmic side of the protein, and affect the dynamics of internal water molecules. The sensitivity of the active-site interactions on the retinal force-field parameters highlights the coupling between the retinal molecule and its immediate protein environment.
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Papers by Ana-nicoleta Bondar