Article
Biochemistry & Molecular Biology
Lisa R. Knoke, Jannik Zimmermann, Natalie Lupilov, Jannis F. Schneider, Beyzanur Celebi, Bruce Morgan, Lars I. Leichert
Summary: The thiol redox balance in the periplasm of E. coli was examined using genetically encoded redox probes (roGFP2 and roGFP-iL). The presence of an alternative system for the introduction of disulfide bonds and the role of glutathione in the oxidative folding machinery were explored.
Review
Biochemistry & Molecular Biology
Sabrina L. Slater, Despoina A. I. Mavridou
Summary: Protein folding is crucial for biological function and recombinant protein production, and the correct formation of disulfide bonds is essential for protein stability. In bacterial expression systems, the limitations of endogenous posttranslational modification systems can hinder the production of proteins with their native folds.
MOLECULAR MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Fenggui Fan, Hao Zhang, Qian Wei, Yahui Wei
Summary: This study reveals the evolutionary conservation of PDI-S between land plants and algal organisms, and elucidates the induction mechanism of AtPDI11 under ER stress and the crucial importance of the D domain for its activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Alessandra Fraternale, Marta De Angelis, Riccardo De Santis, Donatella Amatore, Sofia Masini, Francesca Monittola, Michele Menotta, Federica Biancucci, Francesca Bartoccini, Michele Retini, Valentina Fiori, Raoul Fioravanti, Fabio Magurano, Laura Chiarantini, Florigio Lista, Giovanni Piersanti, Anna T. Palamara, Lucia Nencioni, Mauro Magnani, Rita Crinelli
Summary: The life cycle of SARS-CoV-2 is influenced by the environmental redox state, with a reducing environment impairing spike protein binding to ACE2 and an oxidizing environment promoting their interaction. Synthetic low molecular weight thiols induce a more reduced state in the receptor binding domain of the spike protein, impairing ACE2 binding and interfering with protein folding and viral replication. These thiols could potentially serve as innovative anti-SARS-CoV-2 therapeutics.
Article
Biochemistry & Molecular Biology
Shunsuke Okada, Motonori Matsusaki, Masaki Okumura, Takahiro Muraoka
Summary: This study investigated the influence of a spacer between thiol and guanidyl units on oxidative protein folding, revealing that a conjugate with a diethylene glycol spacer showed lower folding promotion effect. The reduced efficiency was likely due to the lower acidity and more reductive property of the thiol group compared to the conjugate without the spacer. This suggests that the spacer between thiol and guanidyl groups plays a critical role in promoting oxidative protein folding.
Article
Biochemistry & Molecular Biology
Fang Cheng, Qianzhao Ji, Lu Wang, Chih-chen Wang, Guang-Hui Liu, Lei Wang
Summary: This study found that the accumulation of disulfide bonds, which are generated during oxidative protein folding, in aged human mesenchymal stem cells (hMSCs) can be alleviated by deleting protein disulfide isomerase (PDI), a key enzyme involved in oxidative protein folding. The deletion of PDI slows down the rate of oxidative protein folding and reduces the leakage of hydrogen peroxide (H2O2) from the endoplasmic reticulum (ER) into the nucleus, consequently decreasing the expression of SERPINE1, a key driver of cell senescence. Additionally, depletion of PDI also alleviates senescence in various cell models of aging. These findings reveal the previously unknown role of oxidative protein folding in promoting cell aging and provide a potential target for intervention in aging and aging-related diseases.
Article
Biotechnology & Applied Microbiology
Yang Liu, Xiaona Li, Jiaxin Luo, Tao Su, Meiru Si, Can Chen
Summary: The gene ncgl2478 in Corynebacterium glutamicum encodes the dithiol-disulfide isomerase DsbA enzyme, which is involved in stress resistance by reducing S-mycothiolated mixed disulfides and intramolecular disulfides. Its expression is induced by stress in a SigH-dependent manner and it receives electrons preferentially from the MSH/mycothione reductase/NADPH pathway.
Article
Biology
Motonori Matsusaki, Rina Okada, Yuya Tanikawa, Shingo Kanemura, Dai Ito, Yuxi Lin, Mai Watabe, Hiroshi Yamaguchi, Tomohide Saio, Young-Ho Lee, Kenji Inaba, Masaki Okumura
Summary: The physiological functions of proteins are determined by their unique three-dimensional structures, with conserved disulfide-catalysts and chaperone networks playing a crucial role in correct protein folding and prevention of aggregation. Disruption of these networks is implicated in pathology. Complex formation among PDIs accelerates protein folding and prevents aggregation.
Article
Biochemistry & Molecular Biology
Tomasz Przepiora, Donata Figaj, Aleksandra Bogucka, Jakub Fikowicz-Krosko, Robert Czajkowski, Nicole Hugouvieux-Cotte-Pattat, Joanna Skorko-Glonek
Summary: DsbA oxidoreductase plays a crucial role in introducing disulfide bonds in bacteria, and its absence may result in the loss of virulence. In this study, a D. solani dsbA mutant was constructed, and it was found that the lack of DsbA led to the loss of virulence and affected multiple aspects of bacterial physiology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Carlos Santos-Martin, Geqing Wang, Pramod Subedi, Lilian Hor, Makrina Totsika, Jason John Paxman, Begona Heras
Summary: The DsbA enzyme, as part of the disulfide bond forming system, plays a crucial role in bacterial virulence factor assembly and is a potential target for new virulence blockers. Despite extensive studies on DSB systems in various bacterial species, little is known about how DsbA oxidoreductases recognize and interact with a wide range of substrates.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Biotechnology & Applied Microbiology
Lukas A. A. Rettenbacher, Tobias von der Haar
Summary: This study establishes a novel approach for quantitatively investigating the ability of E. coli to produce disulfide bonds in its proteome. The study shows that the demand for disulfide bonded proteins in E. coli changes significantly under different growth conditions, and predicts under what conditions excess capability is available for recombinant protein production.
MICROBIAL CELL FACTORIES
(2022)
Article
Chemistry, Multidisciplinary
Marc Mora, Stephanie Board, Olivier Languin-Cattoen, Laura Masino, Guillaume Stirnemann, Sergi Garcia-Manyes
Summary: Non-native disulfide bonds are dynamic covalent bridges formed in proteins, which can be detected using mechanical force and are associated with protein function and aggregation diseases.
Review
Biochemistry & Molecular Biology
Rafayel Petrosyan, Abhishek Narayan, Michael T. Woodside
Summary: Single-molecule force spectroscopy (SMFS) is a powerful tool for studying protein folding dynamics, uncovering energy landscapes of folding, complex folding pathways, mechanisms of chaperones in assisting folding, effects of ribosomes on co-translational folding, and monitoring membrane protein folding.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Xunxun Jian, Yong Wu, Zaoli Mei, Xiaopeng Zhu, Dongting Zhangsun, Sulan Luo
Summary: In the synthesis of conotoxins with multiple disulfide bonds, determining the natural disulfide bond connectivities is challenging due to the diverse connectivities formed during oxidative folding. This study focuses on KIIIA, a mu-conotoxin with potent inhibitory activity against Nav1.2 and Nav1.4. The non-natural connectivity pattern of KIIIA exhibits the highest activity. The study optimized the Fmoc solid-phase synthesis of KIIIA using different strategies, finding that random oxidation and selective strategies can produce high yields and ideal isomers. Distributed oxidation with different protecting groups was also explored, indicating the importance of cleavage order for avoiding disulfide bond scrambling. The activity of synthesized isomers on Nav1.4 was tested, providing valuable guidance for future studies on multi-disulfide-bonded peptides.
Article
Microbiology
Jing Xia, Yaru Luo, Mianmian Chen, Yuqing Liu, Zhe Wang, Simin Deng, Jiali Xu, Yue Han, Jing Sun, Lingli Jiang, Houhui Song, Changyong Cheng
Summary: Lmo1059, a DsbA family protein, plays a critical role in oxidative stress tolerance and intracellular infection of L. monocytogenes. It efficiently catalyzes oxidized glutathione reduction and its deletion reduces adhesion and invasion while increasing cell-to-cell spread of L. monocytogenes.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biochemistry & Molecular Biology
Aitor Manteca, Jorg Schonfelder, Alvaro Alonso-Caballero, Marie J. Fertin, Nerea Barruetabena, Bruna F. Faria, Elias Herrero-Galan, Jorge Alegre-Cebollada, David De Sancho, Raul Perez-Jimenez
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2017)
Review
Chemistry, Multidisciplinary
Joerg Schonfelder, Alvaro Alonso-Caballero, David De Sancho, Raul Perez-Jimenez
CHEMICAL SOCIETY REVIEWS
(2018)
Article
Multidisciplinary Sciences
Alvaro Alonso-Caballero, Jorg Schonfelder, Simon Poly, Fabiano Corsetti, David De Sancho, Emilio Artacho, Raul Perez-Jimenez
NATURE COMMUNICATIONS
(2018)
Article
Chemistry, Physical
David De Sancho, Jorg Schonfelder, Robert B. Best, Raul Perez-Jimenez, Victor Munoz
JOURNAL OF PHYSICAL CHEMISTRY B
(2018)
Article
Multidisciplinary Sciences
Fabiano Corsetti, Alvaro Alonso-Caballero, Simon Poly, Raul Perez-Jimenez, Emilio Artacho
ROYAL SOCIETY OPEN SCIENCE
(2020)
Article
Nanoscience & Nanotechnology
Karina Ashurbekova, Kristina Ashurbekova, Borja Alonso-Lerma, Iva Saric, Leire Barandiaran, Evgeny Modin, Mladen Petravic, Raul Perez-Jimenez, Mato Knez
Summary: Silicon-based polymers have great potential for applications in biomedicine, nanotechnology, tissue targeting, and drug delivery. A solvent-free molecular layer deposition (MLD) process has been developed to grow environmentally stable hybrid alumosilazane thin films. These films exhibit exceptional biocompatibility and can be used as functional coatings for scaffolds or implantable devices with complex topologies or high-aspect-ratio structures.
ACS APPLIED NANO MATERIALS
(2022)
Article
Microbiology
Borja Alonso-Lerma, Ylenia Jabalera, Sara Samperio, Matias Morin, Almudena Fernandez, Logan T. Hille, Rachel A. Silverstein, Ane Quesada-Ganuza, Antonio Reifs, Sergio Fernandez-Penalver, Yolanda Benitez, Lucia Soletto, Jose A. Gavira, Adrian Diaz, Wim Vranken, Avencia Sanchez-Mejias, Marc Guell, Francisco J. M. Mojica, Benjamin P. Kleinstiver, Miguel A. Moreno-Pelayo, Lluis Montoliu, Raul Perez-Jimenez
Summary: Research reveals that ancient Cas9 protein from extinct bacteria exhibit significant differences in guide RNA and protospacer-adjacent motif requirements compared to modern Cas9 enzymes. Additionally, these ancient Cas9 proteins evolved from nickase to double-strand break activity, have high activity with single-stranded DNA and RNA targets, and are capable of gene editing in human cells.
NATURE MICROBIOLOGY
(2023)
Article
Physics, Multidisciplinary
Antonio Reifs, Irene Ruiz Ortiz, Amaia Ochandorena Saa, Jorg Schonfelder, David De Sancho, Victor Munoz, Raul Perez-Jimenez
Summary: Ultrafast folding proteins have low energetic barriers and fast kinetics, making them suitable for study by both experiments and simulations. However, single molecule force spectroscopy experiments on these proteins are challenging due to the lack of mechanical fingerprints. In this study, the unfolding of an ultrafast protein is investigated using atomic force microscopy experiments.
COMMUNICATIONS PHYSICS
(2023)
Article
Materials Science, Multidisciplinary
Leire Barandiaran, Borja Alonso-Lerma, Antonio Reifs, Izaskun Larraza, Raquel Olmos-Juste, Alba Fernandez-Calvo, Ylenia Jabalera, Arantxa Eceiza, Raul Perez-Jimenez
Summary: Enzymes are capable of converting low-value biomass into high-tech materials, with one particular enzyme being able to synthesize chitin nanocrystals for cell growth and conducting bioinks. The development of strategies for enzymatic conversion of biomass into high-value materials has the potential to expand the applications of enzymes and enzyme design techniques.
COMMUNICATIONS MATERIALS
(2022)
Article
Materials Science, Multidisciplinary
Borja Alonso-Lerma, Leire Barandiaran, Lorena Ugarte, Izaskun Larraza, Antonio Reifs, Raquel Olmos-Juste, Nerea Barruetabena, Iban Amenabar, Rainer Hillenbrand, Arantxa Eceiza, Raul Perez-Jimenez
COMMUNICATIONS MATERIALS
(2020)
Article
Chemistry, Multidisciplinary
Nerea Barruetabena, Borja Alonso-Lerma, Albert Galera-Prat, Nadeem Joudeh, Leire Barandiaran, Leire Aldazabal, Maria Arbulu, Miguel Alcalde, David De Sancho, Jose A. Gavira, Mariano Carrion-Vazquez, Raul Perez-Jimenez
COMMUNICATIONS CHEMISTRY
(2019)
Meeting Abstract
Biophysics
A. Reifs, J. Schonfelder, E. San Sebastian, R. Perez-Jimenez
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
(2019)
Article
Chemistry, Multidisciplinary
Jorg Schonfelder, David De Sancho, Ronen Berkovich, Robert B. Best, Victor Munoz, Raul Perez-Jimenez
COMMUNICATIONS CHEMISTRY
(2018)
Meeting Abstract
Biophysics
A. Manteca, A. Alonso-Caballero, M. Fertin, S. Poly, D. de Sancho, R. Perez-Jimenez
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
(2017)
Meeting Abstract
Biochemistry & Molecular Biology
D. De Sancho, J. Schonfelder, R. Best, V. Munoz, R. Perez-Jimenez