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Talk - Dr. Patricia Saura & Prof. Boris Musset

Nov 28, 2022 | 03:00 PM c.t. - 05:30 PM

The SFB 1078 kindly invites you to the following colloquium talks:

1. Dr. Patricia Saura hosted by Prof. Joachim Heberle (FUB):

Title: Molecular principles of water-gated proton transfer reactions in cytochrome c oxidase

Cytochrome c oxidase (CcO) functions as the terminal electron acceptor in the respiratory chain, catalyzing the reduction of oxygen to water that couples to proton pumping across the membrane. However, the molecular principles of how CcO sorts protons along the pumping and chemical pathways, and how the proton uptake is regulated, remain poorly understood. In this talk, I will present our recent results on the molecular gating principles in proton transfer reactions in CcO. Using a combination of large-scale quantum chemical DFT calculations, hybrid quantum/classical (QM/MM) simulations, and molecular dynamics (MD) explorations, we show that redox reactions coupled to conformational changes generate oriented electric fields around the CcO active site that direct the protons along the chemical and pumping pathways. These principles apply similarly to proton transfer along the proton-conducting D- and K-channels. By combining our multiscale computational approach with biophysical and structural experiments, we also show that proton uptake via the K-channel is modulated by lipid interactions at regulatory sites that couple to key conformational changes at the K-channel entrance. Our mechanistic principles show distinct similarities with other energy converting enzyme complexes, suggesting that electric fields modulate catalysis in enzyme reactions, and the relevance of lipid interactions in bioenergetic complexes.

2. Prof. Boris Musset hosted by Dr. Jacek Kozuch (FUB):

Title: The voltage-gated proton channel (HV) discovers its family, and a detailed investigation of pH-dependent gating.

The voltage-gated proton channel HV has been found in a multitude of species ranging from humans, over fish, insects, algae, to acidians and even dinoflagellates. In all these species exclusively a single gene coded for the voltage-gated proton channel. The one gene per species rule appeared to be a dogma representing voltage-gated proton channels. Recently, we discovered the genes of three paralogs of HV (HV1, HV2, HV3) in Aplysia californica, a common model organism of neurobiology. All three paralogs have distinct biophysical properties. Intriguingly, AcHV3 permeates a prominent proton selective leak current. The voltage gating of HV is strongly coupled to the pH gradient across the plasma membrane. Recently, we investigated pH-dependent gating of HV1 using constant pH MD simulations in symmetrical and asymmetrical pH conditions across the membrane. In our study, the pKa of every titratable amino acid was assessed in single simulations. The simulations show initial conformational changes between a deactivated and activated state of HV1, solely by changing the inside or outside pH.

Time & Location

Nov 28, 2022 | 03:00 PM c.t. - 05:30 PM

Hörsaal B, FB Physik FUB, Arnimallee 14, 14195 Berlin