Article
Chemistry, Multidisciplinary
Kaushik Pal, Ying Tu, Xuefeng Wang
Summary: Podosomes are integrin-mediated cell adhesion units involved in various cellular and physiological processes. Their formation is influenced by actomyosin contractility and actin polymerization, while extracellular integrin-ligand tensions are not crucial for their formation.
Article
Physiology
Yi-Ting Huang, Ya-Ting Hsu, Yih-Fung Chen, Meng-Ru Shen
Summary: Store-operated Ca2+ entry (SOCE) is essential for cellular functions, with STIM1 playing a crucial role in this process. STIM1 mutations have been shown to impact cancer cell behavior, with specific variants affecting focal adhesion turnover, Ca2+ influx during SOCE, and cell migration, suggesting potential therapeutic implications.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Hongbin Li
Summary: Metalloproteins play crucial roles in biological processes. Single-molecule force spectroscopy is a powerful tool to investigate the folding and unfolding mechanisms of metalloproteins at the single-molecule level, providing insights into their functions and dynamics. Experimental studies of metalloprotein folding are challenging, but single-molecule force spectroscopy has allowed researchers to directly probe the folding and unfolding processes and the impact of metal centers.
Article
Multidisciplinary Sciences
Jonathan Yaacov Weinstein, Carlos Marti-Gomez, Rosalie Lipsh-Sokolik, Shlomo Yakir Hoch, Demian Liebermann, Reinat Nevo, Haim Weissman, Ekaterina Petrovich-Kopitman, David Margulies, Dmitry Ivankov, David M. McCandlish, Sarel J. Fleishman
Summary: Mutations in a protein's active site can lead to dramatic and useful changes in protein activity. However, due to a high density of molecular interactions, the active site is sensitive to mutations, making it difficult to obtain functional multipoint mutants. A new approach called high-throughput Functional Libraries (htFuncLib) has been introduced to design a sequence space where mutations can form low-energy combinations, reducing the risk of incompatible interactions. This approach has been successfully applied to GFP, resulting in the discovery of thousands of unique designs with improved functional properties.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Shengchao Shi, Tao Wu, Peng Zheng
Summary: Cobalt is a trace transition metal that exists in numerous cobalt-containing proteins in living organisms. The Co(II) ion can be used as a powerful tool to characterize metal-binding proteins through the formation of cobalt-ligand bonds. This study used atomic force microscopy-based single-molecule force spectroscopy to directly measure the rupture force of the Co(II)-thiolate bond in cobalt-substituted rubredoxin. The results showed that the Co(II)-thiolate bond is a mechanically stable chemical bond, and the Co-S bond is less stable compared to the Zn-S bond in proteins.
Article
Chemistry, Multidisciplinary
Haipei Liu, Zhaowei Liu, Mariana Sa Santos, Michael A. A. Nash
Summary: Single-molecule force spectroscopy (SMFS) is a powerful tool for studying protein folding and mechanical properties. However, the traditional method of immobilization using lysine residues results in a heterogeneous distribution of tether positions. In this study, we compared lysine-based immobilization to site-specific immobilization using genetically encoded peptide tags (ybbR). Our results showed that lysine-based immobilization led to signal deterioration and incorrect classification of unfolding pathways. We also developed a mixed immobilization approach that partially recovered specific signals.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Chemistry, Multidisciplinary
Rahul Banerjee, John D. Lipscomb
Summary: Rigorous substrate selectivity in enzyme catalysis is attributed to the favorable process of substrate binding to the enzyme active site based on complementary physiochemical characteristics. However, this selectivity becomes more difficult to rationalize for diminutive molecules with too narrow a range of physical characteristics.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Article
Chemistry, Inorganic & Nuclear
Irene R. A. M. Ogutu, Richard C. Holz, Brian Bennett
Summary: Research has shown that an eight amino acid peptide based on the metal binding motif of Co-type nitrile hydratase from Pseudonocardia thermophilia can coordinate Fe(II) under anaerobic conditions. Exposure to air results in the formation of a low-spin Fe(III)-peptide complex, similar to the nitrile hydratase from Rhodococcus equi TG328-2.
INORGANIC CHEMISTRY
(2021)
Article
Chemistry, Physical
Iman Abdoli, Abhinav Sharma
Summary: Equilibrium properties of passively diffusing particles in an external magnetic field are not affected by Lorentz force, while active Brownian particles exhibit steady-state phenomena that depend on the applied magnetic field's strength and polarity. Through stochastic resetting, an active system transitions into a stationary state characterized by non-uniform density distribution and bulk fluxes perpendicular to density gradients, with novel features emerging in the presence of an inhomogeneous magnetic field. Theoretical predictions are validated using Brownian dynamics simulations, showing that active particles exhibit non-monotonic density distribution at lower resetting rates and take longer to reach a target point when the magnetic field increases away from the axis.
Article
Chemistry, Multidisciplinary
Maria Alessandra Martini, Konstantin Bikbaev, Yunjie Pang, Christian Lorent, Charlotte Wiemann, Nina Breuer, Ingo Zebger, Serena DeBeer, Ingrid Span, Ragnar Bjornsson, James A. Birrell, Patricia Rodriguez-Macia
Summary: [FeFe] hydrogenase variants with a mutation in the proton transfer pathway can form two new active site states with a CN- ligand bound to the apical position of [2Fe](H). These states can be generated by either cannibalization from damaged [2Fe](H) subclusters or addition of exogenous CN-. This study provides the first detailed characterization of the interaction between exogenous CN- and [FeFe] hydrogenases.
Article
Chemistry, Physical
Tao He, Matthias Stolte, Yan Wang, Rebecca Renner, P. Paul Ruder, Frank Wuerthner, C. Daniel Frisbie
Summary: Chemical doping strategy for organic semiconductors targeting crystallographic step edges leads to significant improvement in electron transport properties, with a tenfold increase in electron mobility and a switch from thermally activated to band-like behaviour. This approach provides evidence for doping-induced space charge and suggests new site-specific doping strategies for organic semiconductors, deviating from traditional randomly distributed substitutional impurities. The presence of doping-induced electron atmospheres in organic systems is confirmed, aligning with expectations from conventional solid-state theory.
Article
Chemistry, Multidisciplinary
Jing-Yuan Nie, Guo-Bin Song, Yi-Bing Deng, Peng Zheng
Summary: This study measured the stability of the outer mitochondrial membrane protein mitoNEET (mNT) and its cluster at different pH values using single-molecule force spectroscopy. The results showed that the behavior of the protein is consistent in both weakly acidic and basic solutions, despite the presence of a labile Fe-N bond.
Article
Chemistry, Multidisciplinary
Amir Hatamie, Lin Ren, Haiqiang Dou, Nikhil R. Gandasi, Patrik Rorsman, Andrew Ewing
Summary: The research shows that vesicular release in pancreatic beta cells is not all-or-none, but rather partial release of insulin and serotonin. Utilizing nanoscale amperometric chemical methods, the study quantified the amount of serotonin stored and released during each exocytosis event, revealing that beta cells only release one-third of their granule content. This has implications for understanding type-2 diabetes.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Multidisciplinary Sciences
Kathryn H. Gunn, Saskia B. Neher
Summary: Lipoprotein lipase (LPL) hydrolyzes triglycerides from circulating lipoproteins, and the structure of an active LPL dimer reveals a hydrophobic pore adjacent to the active site. The dimerization interface and pore may play a role in substrate specificity and acyl chain release from LPL.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Eric M. Mulhall, Andrew Ward, Darren Yang, Mounir A. Koussa, David P. Corey, Wesley P. Wong
Summary: Researchers characterized the strength of the tip-link connection at single-molecule resolution and found that a single tip-link bond is more mechanically stable relative to classic cadherins, and that the double stranded tip-link connection is stabilized by single strand rebinding facilitated by strong cis-dimerization domains.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Physical
Jingyuan Nie, Yibing Deng, Fang Tian, Shengchao Shi, Peng Zheng
Summary: Cation-pi interaction plays a crucial role in biological systems but its experimental verification and quantification at the molecular level are limited. In this study, atomic force microscopy-based single-molecule force spectroscopy was used to measure the stability and kinetics of NGAL protein with cation-pi interactions. The results demonstrated the high-precision detection of weak cation-pi interaction in NGAL.
Article
Chemistry, Physical
Dongdong Wu, Hai Lei, Xian Xie, Liang Zhou, Peng Zheng, Yi Cao, Yan Zhang
Summary: This study developed a double network hydrogel that mimics protein assemblies in the extracellular matrix (ECM) and defines its mechanical and biochemical cues using advanced chemical biology tools.
Article
Chemistry, Multidisciplinary
Shengchao Shi, Ziyi Wang, Yibing Deng, Fang Tian, Qingsong Wu, Peng Zheng
Summary: In this study, a protein immobilization method combining SPAAC click reaction and enzymatic ligation is developed to overcome the issues of NHS hydrolysis and nonspecific reaction of maleimide with the protein. The successful immobilization of eGFP and verification of its correct folding and stability demonstrate that this method is stable, efficient, and site-specific.
Article
Biochemistry & Molecular Biology
Shengchao Shi, Tao Wu, Peng Zheng
Summary: Cobalt is a trace transition metal that exists in numerous cobalt-containing proteins in living organisms. The Co(II) ion can be used as a powerful tool to characterize metal-binding proteins through the formation of cobalt-ligand bonds. This study used atomic force microscopy-based single-molecule force spectroscopy to directly measure the rupture force of the Co(II)-thiolate bond in cobalt-substituted rubredoxin. The results showed that the Co(II)-thiolate bond is a mechanically stable chemical bond, and the Co-S bond is less stable compared to the Zn-S bond in proteins.
Article
Biochemistry & Molecular Biology
Tianyu Duan, Qingyuan Bian, Hongbin Li
Summary: Fluorescent polymeric hydrogels are promising information storage media that can generate fluorescent patterns in a light-controlled and spatially defined manner. Grayscale patterning allows the generation of multi-dimensional fluorescent images. This method opens up new possibilities for developing protein-based smart materials for information storage and anti-counterfeit applications.
Article
Chemistry, Physical
Ziyi Wang, Zhongxing Zhao, Guoqiang Li, Peng Zheng
Summary: The de novo-designed metalloprotein alpha 3DIV binds to mercury via three cysteine residues under dynamic conditions. An unusual trigonal three-coordinate HgS3 site is formed in the protein in basic solution, whereas a linear two-coordinate HgS2 site is formed in acidic solution. It is found that any two of the three cysteines in the protein bind to mercury in the HgS2 site.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Qun Ma, Boqiang He, Guojin Tang, Ran Xie, Peng Zheng
Summary: The immobilization of proteins on nanoparticles has gained attention in recent years. Enzymatic protein immobilization, particularly using the peptide ligase OaAEP1, shows advantages due to site-specific connection. Our study demonstrates the successful C-terminal site-specific protein immobilization on amino-functionalized Fe3O4 nanoparticles mediated by OaAEP1. This provides a new method for site-specific protein immobilization on nanoparticles.
Article
Biochemistry & Molecular Biology
Zhiyi Wang, Mengdie Wang, Zhongxin Zhao, Peng Zheng
Summary: Carboxylate-bridged diiron proteins are a family of proteins involved in various physiological processes. These proteins have a conserved EXXH motif that forms the carboxylate bridge and is crucial for metal binding. In this study, we used a de novo-designed single-chain di-ferri protein (DFsc) with two EXXH motifs as a model protein to investigate the stability of the carboxylate-bridged di-metal binding site. By using atomic force microscopy-based single-molecule force spectroscopy, we obtained the mechanical and kinetic properties of the di-Zn site in DFsc. The results demonstrate the mechanical stability of the carboxylate-bridged di-metal site and enhance our understanding of this important type of metalloprotein.
Article
Chemistry, Physical
Ziyi Wang, Zhongxing Zhao, Zeyue Yang, Guoqiang Li, Peng Zheng
Summary: Lead is a toxic metal widely used in human society, but its interaction with proteins and formation of Pb-S bonds can cause toxicity. In this study, we used a de novo designed protein alpha 3DIV as a model protein to study Pb-S bonds. By detecting specific Pb-S bond rupture signals using atomic force microscopy-based single-molecule force spectroscopy (AFM-SMFS), we confirmed the formation of a triangular pyramidal PbS3 site in alpha 3DIV, including the previously undetected Pb-S(Cys67) bond. We also revealed and quantified the pH-dependent weakening of Pb-S bond strength, resulting in the dissociation of the PbS3 site at pH 4.5.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Chemistry, Physical
Jingyuan Nie, Ziyi Wang, Mengdie Wang, Peng Zheng
Summary: The specific interaction between Ni-nitrilotriaceticacid and the six-histidine tag is widely used in biological research for recombinant protein purification. The stability of this interaction is crucial for target protein binding, while the mechanochemistry between the system and the competing ligand imidazole/proton remains unclear. In this study, an AFM-SMFS system was used to characterize the system and reveal the destabilizing effect of imidazole and proton on the interaction, leading to a 3-fold increase in the bond dissociation rate.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Engineering, Electrical & Electronic
Songlin Zhang, Yihao Zhou, Alberto Libanori, Yibing Deng, Mingyang Liu, Mengjuan Zhou, Hao Qu, Xun Zhao, Peng Zheng, You-Liang Zhu, Jun Chen, Swee Ching Tan
Summary: Soft, conductive fibres for electronic textiles can be made using a spontaneous phase separation technique inspired by spider silk formation. These fibres are mechanically stretchable, strong, and electrically conductive, making them suitable for various applications including energy, sensing, and therapeutic uses.
NATURE ELECTRONICS
(2023)
Article
Chemistry, Multidisciplinary
Bin Zheng, Yuelong Xiao, Bei Tong, Yutong Mao, Rui Ge, Fang Tian, Xianchi Dong, Peng Zheng
Summary: A cluster of newly occurring mutations on Omicron was found in the β-core region of the spike protein's receptor-binding domain, where mutations rarely occurred before. The mechanical stability of Omicron RBD was found to increase by approximately 20% compared to the wild type. Molecular dynamics simulations showed that Omicron RBD had more hydrogen bonds in the β-core region due to the closing of the α-helical motif caused by the S373P mutation. In addition, the dissociation force between Omicron RBD and ACE2 was higher. This study reveals the mechanically stabilizing effect of the conserved S373P mutation in Omicron and the possible evolutionary trend of the β-core region of the receptor-binding domain.
Article
Chemistry, Physical
Ziyi Wang, Zhongxing Zhao, Zeyue Yang, Guoqiang Li, Peng Zheng
Summary: Lead is a toxic metal that is harmful to human beings due to its long history and wide use in human society. It exerts toxicity through its interaction with proteins, particularly by targeting thiol-rich proteins and forming stable Pb-S bonds. A study was conducted using a de novo designed protein alpha 3DIV as a model protein to investigate Pb-S bonds. Atomic force microscopy-based single-molecule force spectroscopy (AFM-SMFS) was used to detect specific Pb-S bond rupture signals, revealing the formation of a triangular pyramidal PbS3 site in alpha 3DIV and the pH-dependent weakening of Pb-S bond strength.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Biochemistry & Molecular Biology
Xuan Ding, Ziyi Wang, Bin Zheng, Shengchao Shi, Yibing Deng, Hanyang Yu, Peng Zheng
Summary: Enzymatic protein ligation is a powerful and widely used method for studying protein mechanics. However, it requires multiple steps and expertise. To overcome this, we simplified the procedure using two strategies based on AEP.
RSC CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Zhangwei Lu, Yutong Liu, Yibing Deng, Bin Jia, Xuan Ding, Peng Zheng, Zhe Li
Summary: We describe the use of a protein ligase for covalently attaching a protein to a peptide nucleic acid (PNA). This approach only requires a GL dipeptide at the N-terminus of the target protein and an NGL tripeptide at the C-terminus of the PNA. Our study demonstrates the versatility of this method by successfully attaching a PNA strand to three different proteins. Additionally, we show the feasibility of erasable imaging of EGFR on HEK293 cell membranes using DNA origami nanostructures and toehold-mediated strand displacement.
CHEMICAL COMMUNICATIONS
(2022)