Biology subjects

Poverlein, M. C.

Publications and source records attributed to Poverlein, M. C..

3 recordsLinked to original sources

bioRxiv2024

Protein-Induced Membrane Strain Drives Supercomplex Formation

Mitochondrial membranes harbor the electron transport chain (ETC) that powers oxidative phosphorylation (OXPHOS) and drives the synthesis of ATP. Yet, under physiological conditions, the OXPHOS proteins operate as higher-order supercomplex (SC) assemblies, although their functional role remains poorly understood and much debated. By combining large-scale atomistic and coarse-grained molecular simulations with analysis of cryo-electron microscopic data and statistical as well as kinetic models, we show here that the formation of the mammalian I/III2 supercomplex reduces the molecular strain of inner mitochondrial membranes by altering the local membrane thickness and leading to an accumulation of both cardiolipin and quinone around specific regions of the SC. We find that the SC assembly also affects the global motion of the individual ETC proteins with possible functional consequences. On a general level, our findings suggest that molecular crowding and strain effects provide a thermodynamic driving force for the SC formation, with a possible flux enhancement in crowded biological membranes under constrained respiratory conditions. Significance StatementThe membrane-bound proteins of respiratory chains power oxidative phosphorylation (OXPHOS) and drive the synthesis of ATP. However, recent biochemical and structural data show that the OXPHOS proteins operate as higher-order supercomplex assemblies for reasons that remain elusive and much debated. Here we show that the mammalian respiratory supercomplexes reduce the molecular strain of inner mitochondrial membranes and enhance the allosteric crosstalk by altering the protein dynamics with important biochemical and physiological implications.

biophysics↗

bioRxiv2024

Modified Chlorophyll Pigment at ChlD1 Tunes Photosystem II Beyond the Red-Light Limit

Photosystem II (PSII) is powered by the light-capturing properties of chlorophyll a pigments that define the spectral range of oxygenic photosynthesis. Some photosynthetic cyanobacteria can acclimate to growth in longer wavelength light by replacing five chlorophylls for long wavelength pigments in specific locations, including one in the reaction center (RC). However, the exact location and the nature of this long wavelength pigment still remain uncertain. Here we have addressed the color-tuning mechanism of the farred light PSII (FRL-PSII) by excited state calculations at both the ab initio correlated (ADC2) and linear-response time-dependent density functional theory (LR-TDDFT) levels in combination with large-scale hybrid quantum/classical (QM/MM) simulations and atomistic molecular dynamics. We show that substitution of a single chlorophyll pigment (ChlD1) at the RC by chlorophyll d leads to a spectral shift beyond the far-red light limit, as a result of the protein electrostatic, polarization and electronic coupling effects that reproduce key structural and spectroscopic observations. Pigment substitution at the ChlD1 site further results in a low site energy within the RC that could function as a sink for the excitation energy and initiate the primary charge separation reaction, driving the water oxidation. Our findings provide a basis for understanding color-tuning mechanisms and bioenergetic principles of oxygenic photosynthesis at the far-red light limit.

biophysics↗

bioRxiv2024

Mechanism of Proton Release during Water Oxidation in Photosystem II

Photosystem II (PSII) catalyzes the light-driven water oxidation that releases dioxygen into our atmosphere and provides the electrons needed for the synthesis of biomass. The catalysis occurs in the oxygen-evolving oxo-manganese-calcium (Mn4O5Ca) cluster that drives the stepwise oxidation and deprotonation of substrate water molecules leading to the O2 formation. However, despite recent advances, the mechanism of these reactions remains unclear and much debated. Here we show that the light-driven Tyr161D1 oxidation adjacent to the Mn4O5Ca cluster, significantly decreases the barrier for proton transfer from the putative substrate water molecule (W3/Wx) to Glu310D2, which is accessible to the luminal bulk. By combining hybrid quantum/classical (QM/MM) free energy calculations with atomistic molecular dynamics (MD) simulations, we probe the energetics of the proton transfer along the Cl1 pathway. We demonstrate that the proton transfer occurs via water molecules and a cluster of conserved carboxylates, driven by redox-triggered electric fields directed along the pathway. Glu65D1 establishes a local molecular gate that controls the proton transfer to the luminal bulk, whilst Glu312D2 acts as a local proton storage site. The identified gating region could be important in preventing back-flow of protons to the Mn4O5Ca cluster. The structural changes, derived here based on the dark-state PSII structure, strongly support recent time-resolved XFEL data of the S3[->]S4 transition (Nature 617, 2023), and reveal the mechanistic basis underlying deprotonation of the substrate water molecules. Our combined findings provide insight into the water oxidation mechanism of PSII and show how the interplay between redox-triggered electric fields, ion-pairs, and hydration effects control proton transport reactions. Significance StatementPhotosystem II is natures water splitting enzyme that produces the oxygen in the atmosphere and drives the synthesis of biomass. The water splitting reaction releases protons to the luminal bulk contributing to the protonmotive force that drives the synthesis of ATP. Key mechanistic principles of the light-driven water splitting reaction remain debated, amongst them the catalytically important deprotonation steps. Here we show how the oxygen-evolving oxo-manganese-calcium cluster transports protons via conserved carboxylates and water molecules in proton arrays that lead to the luminal bulk. We identify a local proton storage site and molecular gates that prevent wasteful back reactions by undergoing conformational changes, and we show how electric field effects control the protonation dynamics in Photosystem II.

biophysics↗