Han Sun

Technische Universität Berlin

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Tillmann Utesch

Leibniz-Forschungsinstitut für Molekulare Pharmakologie

Songhwan Hwang

Leibniz-Forschungsinstitut für Molekulare Pharmakologie

Peter Hegemann

Humboldt-Universität zu Berlin

Adam Lange

Leibniz-Forschungsinstitut für Molekulare Pharmakologie

Bert L. de Groot

Max Planck Institute for Dynamics and Self-Organization

Jens Balke

Freie Universität Berlin

Francisco Velázquez Escobar

Technische Universität Berlin

Zhaoxu Wang

Bureau of Geology and Mineral Exploration and Development of Guizhou Province

Junpeng Li

Shanxi University of Traditional Chinese Medicine

Shaofei Wang

Yancheng Institute of Technology

Cooperative Institutions

Leibniz-Forschungsinstitut für Molekulare Pharmakologie

Humboldt-Universität zu Berlin

Freie Universität Berlin

Czech Academy of Sciences, Institute of Physiology

Charité - Universitätsmedizin Berlin

Kiel University

Chinese Academy of Sciences

Max Planck Society

Leibniz Association

Jena University Hospital

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

QuasAr Odyssey: the origin of fluorescence and its voltage sensitivity in microbial rhodopsins

Nature Communications (2022)

Arita Silapetere Songhwan Hwang Yusaku Hontani Rodrigo G. Fernandez Lahore Jens Balke

Abstract Rhodopsins had long been considered non-fluorescent until a peculiar voltage-sensitive fluorescence was reported for archaerhodopsin-3 (Arch3) derivatives. These proteins named QuasArs have been used for imaging membrane voltage changes in cell cultures and small animals. However due to the low fluorescence intensity, these constructs require use of much higher light intensity than other optogenetic tools. To develop the next generation of sensors, it is indispensable to first understand the molecular basis of the fluorescence and its modulation by the membrane voltage. Based on spectroscopic studies of fluorescent Arch3 derivatives, we propose a unique photo-reaction scheme with extended excited-state lifetimes and inefficient photoisomerization. Molecular dynamics simulations of Arch3, of the Arch3 fluorescent derivative Archon1, and of several its mutants have revealed different voltage-dependent changes of the hydrogen-bonding networks including the protonated retinal Schiff-base and adjacent residues. Experimental observations suggest that under negative voltage, these changes modulate retinal Schiff base deprotonation and promote a decrease in the populations of fluorescent species. Finally, we identified molecular constraints that further improve fluorescence quantum yield and voltage sensitivity.

Quantum yield

10.1038/s41467-022-33084-4

Cite

Citations (20)

High Voltage Stable Polyoxalate Catholyte with Cathode Coating for All‐Solid‐State Li‐Metal/NMC622 Batteries

Advanced Energy Materials (2020)

Xiangyu Pan Han Sun Zhaoxu Wang Hao Huang Qian Chang

Abstract The solid polymer electrolyte (SPE) is one type of the most promising solid‐state electrolytes for next‐generation solid‐state batteries, due to its good compatibility with Li‐metal, high flexibility, and safety. To compete with currently used conventional Li‐ion batteries in energy density, SPEs must be integrated with high energy density cathode of LiNi x Mn y Co z O 2 ( x + y + z = 1, 0.5 < x < 1) (NMC). However, the application of SPEs with NMC is limited by the narrow redox window of single SPEs and interfacial decomposition of SPEs by NMC. To overcome these challenges, a strategy is proposed utilizing a polymeric‐catholyte/‐anolyte‐composed dual‐polymer electrolyte and a cathode coating: a low voltage stable polyether works as a separator and stabilizes the interface with Li‐metal, while a high voltage stable polyoxalate functions as the catholyte and NMC particles are precoated by TiO 2 . This cell model not only widens the voltage window of the electrolyte system, but also protects the polyoxalate in the cathode from interfacial decomposition. With this strategy, cycling stability of all‐solid‐state Li‐metal/LiNi 0.6 Mn 0.2 Co 0.2 O 2 (NMC622) cells is significantly improved. Meanwhile, large volume expansions of deposited lithium on both the Li‐metal anode and the copper collector are observed, which deserve more attention in the investigation of all‐solid‐state cells.

Separator (oil production)

Fast ion conductor

Electrochemical window

10.1002/aenm.202002416

Cite

Citations (60)

Atomistic mechanism of coupling between cytosolic sensor domain and selectivity filter in TREK K2P channels

Nature Communications (2024)

Berke Türkaydin Marcus Schewe Elena B. Riel Friederike Schulz Johann Biedermann

Abstract The two-pore domain potassium (K 2P ) channels TREK-1 and TREK-2 link neuronal excitability to a variety of stimuli including mechanical force, lipids, temperature and phosphorylation. This regulation involves the C-terminus as a polymodal stimulus sensor and the selectivity filter (SF) as channel gate. Using crystallographic up- and down-state structures of TREK-2 as a template for full atomistic molecular dynamics (MD) simulations, we reveal that the SF in down-state undergoes inactivation via conformational changes, while the up-state structure maintains a stable and conductive SF. This suggests an atomistic mechanism for the low channel activity previously assigned to the down state, but not evident from the crystal structure. Furthermore, experimentally by using (de-)phosphorylation mimics and chemically attaching lipid tethers to the proximal C-terminus (pCt), we confirm the hypothesis that moving the pCt towards the membrane induces the up-state. Based on MD simulations, we propose two gating pathways by which movement of the pCt controls the stability (i.e., conductivity) of the filter gate. Together, these findings provide atomistic insights into the SF gating mechanism and the physiological regulation of TREK channels by phosphorylation.

10.1038/s41467-024-48823-y

Cite

Citations (6)

A single NaK channel conformation is not enough for non-selective ion conduction

Nature Communications (2018)

Chaowei Shi Yao He Kitty Hendriks Bert L. de Groot Xiaoying Cai

Abstract NaK and other non-selective channels are able to conduct both sodium (Na + ) and potassium (K + ) with equally high efficiency. In contrast to previous crystallographic results, we show that the selectivity filter (SF) of NaK in native-like lipid membranes adopts two distinct conformations that are stabilized by either Na + or K + ions. The atomic differences of these conformations are resolved by solid-state NMR (ssNMR) spectroscopy and molecular dynamics (MD) simulations. Besides the canonical K + permeation pathway, we identify a side entry ion-conduction pathway for Na + permeation unique to NaK. Moreover, under otherwise identical conditions ssNMR spectra of the K + selective NaK mutant (NaK2K) reveal only a single conformational state. Therefore, we propose that structural plasticity within the SF and the selection of these conformations by different ions are key molecular determinants for highly efficient conduction of different ions in non-selective cation channels.

NAK

10.1038/s41467-018-03179-y

Cite

Citations (64)

The opening dynamics of the lateral gate regulates the activity of rhomboid proteases

Science Advances (2023)

Claudia Bohg Carl Öster Berke Türkaydin Michael Lisurek Pascal Sanchez-Carranza

Rhomboid proteases hydrolyze substrate helices within the lipid bilayer to release soluble domains from the membrane. Here, we investigate the mechanism of activity regulation for this unique but wide-spread protein family. In the model rhomboid GlpG, a lateral gate formed by transmembrane helices TM2 and TM5 was previously proposed to allow access of the hydrophobic substrate to the shielded hydrophilic active site. In our study, we modified the gate region and either immobilized the gate by introducing a maleimide-maleimide (M2M) crosslink or weakened the TM2/TM5 interaction network through mutations. We used solid-state nuclear magnetic resonance (NMR), molecular dynamics (MD) simulations, and molecular docking to investigate the resulting effects on structure and dynamics on the atomic level. We find that variants with increased dynamics at TM5 also exhibit enhanced activity, whereas introduction of a crosslink close to the active site strongly reduces activity. Our study therefore establishes a strong link between the opening dynamics of the lateral gate in rhomboid proteases and their enzymatic activity.

Rhomboid

10.1126/sciadv.adh3858

Cite

Citations (9)

Subunit-specific conductance of single homomeric and heteromeric HCN pacemaker channels at femtosiemens resolution

Proceedings of the National Academy of Sciences (2025)

Klaus Benndorf Uta Enke Debanjan Tewari Jana Kusch Haoran Liu

In mammals, the four subunit isoforms HCN1–4 assemble to form functional homotetrameric and heterotetrameric hyperpolarization-activated cyclic nucleotide-modulated (HCN) ion channels. Despite the outstanding relevance of HCN channels for organisms, including generating electrical rhythmicity in cardiac pacemaker cells and diverse types of brain neurons, key channel properties are still elusive. In particular, the unitary conductance, γ, of HCN channels is highly controversial. We analyzed the unitary conductance at femtosiemens resolution of all four homotetrameric channels of the mouse, mHCN1–4. All conductance values are in the range of 1 pS which is exceptionally small compared to most other ion channels. Surprisingly, the conductance among the isoforms differs up to threefold (γ mHCN2 = 1.54 pS > γ mHCN1 = 0.84 pS > γ mHCN3 = 0.54 pS ≈ γ mHCN4 = 0.51 pS) though the residues in the two narrow parts of the pore, the selectivity filter and the inner gate, are conserved. Mutagenesis and all-atom molecular dynamics simulations demonstrate that the differences in the conductance are generated by different amounts of negative charges in the outer channel vestibule, which control ion accumulation. In line with these results, heterotetrameric channels exhibit intermediate unitary conductance values with respect to the homotetrameric channels. Our approach demonstrates how HCN channels can be functionally differentiated at the single-channel level, paving the way to target specific channels with selective drugs.

Homomeric

HCN channel

10.1073/pnas.2422533122

Cite

Citations (0)

Dual‐Polymer‐Electrolytes: High Voltage Stable Polyoxalate Catholyte with Cathode Coating for All‐Solid‐State Li‐Metal/NMC622 Batteries (Adv. Energy Mater. 42/2020)

Advanced Energy Materials (2020)

Xiangyu Pan Han Sun Zhaoxu Wang Hao Huang Qian Chang

In article number 2002416, Weidong Zhou and co-workers develop a poly-oxalate/poly-ether dual-polymer-electrolyte system to electrochemically tolerate both high potential cathodes and low potential anodes, respectively. Combined with a cathode coating, the interfacial decomposition of poly-oxalate in LiNi0.6Mn0.2Co0.2O2(NMC622) is suppressed. With the help of this strategy, the cycling performance of all-solid-state Li-metal/NMC622 cells is significantly improved.

10.1002/aenm.202070176

Cite

Citations (1)

The conduction pathway of potassium channels is water free under physiological conditions

Science Advances (2019)

Carl Öster Kitty Hendriks Wojciech Kopeć Veniamin Chevelkov Chaowei Shi

Detection of bound water in a potassium channel by solid-state NMR supports the “direct” knock-on ion permeation mechanism.

10.1126/sciadv.aaw6756

Cite

Citations (56)

Nonselective cation permeation in an AMPA-type glutamate receptor

Proceedings of the National Academy of Sciences (2021)

Johann Biedermann Sebastian Braunbeck Andrew J.R. Plested Han Sun

Significance AMPA-type glutamate receptors (AMPARs) make the final step in a relay of excitability from one brain cell to another. The receptor contains an integral ion channel, which, when opened by neurotransmitter, permits sodium and other cations to cross the cell membrane. We investigated permeation of sodium, potassium, and cesium at the atomistic level using a computational molecular dynamics approach and obtained ion transit rates similar to those in wet experiments over tens of microseconds of simulations. We determined that the region selecting between cations is the simplest of any channel of this type. Distinct from ion channels that select single ion species, sodium and potassium remain partly hydrated and have only one major binding site in the channel.

Neurotransmitter receptor

Sodium Glutamate

10.1073/pnas.2012843118

Cite

Citations (26)

Diversity of rhodopsin cyclases in zoospore-forming fungi

Proceedings of the National Academy of Sciences (2023)

Matthias Broser W. F. Busse Anika Spreen Maila Reh Yinth Andrea Bernal Sierra

Light perception for orientation in zoospore-forming fungi is linked to homo- or heterodimeric rhodopsin-guanylyl cyclases (RGCs). Heterodimeric RGCs, first identified in the chytrid Rhizoclosmatium globosum , consist of an unusual near-infrared absorbing highly fluorescent sensitizer neorhodopsin (NeoR) that is paired with a visual light-absorbing rhodopsin responsible for enzyme activation. Here, we present a comprehensive analysis of the distribution of RGC genes in early-branching fungi using currently available genetic data. Among the characterized RGCs, we identified red-sensitive homodimeric RGC variants with maximal light activation close to 600 nm, which allow for red-light control of GTP to cGMP conversion in mammalian cells. Heterodimeric RGC complexes have evolved due to a single gene duplication within the branching of Chytridiales and show a spectral range for maximal light activation between 480 to 600 nm. In contrast, the spectral sensitivity of NeoRs is reaching into the near-infrared range with maximal absorption between 641 and 721 nm, setting the low energy spectral edge of rhodopsins so far. Based on natural NeoR variants and mutational studies, we reevaluated the role of the counterion-triad proposed to cause the extreme redshift. With the help of chimera constructs, we disclose that the cyclase domain is crucial for functioning as homo- or heterodimers, which enables the adaptation of the spectral sensitivity by modular exchange of the photosensor. The extreme spectral plasticity of retinal chromophores in native photoreceptors provides broad perspectives on the achievable spectral adaptation for rhodopsin-based molecular tools ranging from UVB into the near-infrared.

10.1073/pnas.2310600120

Cite

Citations (4)