Article
Multidisciplinary Sciences
Yashpal Rawal, Lijia Jia, Aviv Meir, Shuo Zhou, Hardeep Kaur, Eliza A. Ruben, Youngho Kwon, Kara A. Bernstein, Maria Jasin, Alexander B. Taylor, Sandeep Burma, Robert Hromas, Alexander V. Mazin, Weixing Zhao, Daohong Zhou, Elizabeth V. Wasmuth, Eric C. Greene, Patrick Sung, Shaun K. Olsen
Summary: This study reports cryogenic electron microscopy reconstructions of human BCDX2 in apo and ssDNA-bound states. The structures reveal the participation of the amino-terminal domains of RAD51B, RAD51C and RAD51D in inter-subunit interactions for complex formation and ssDNA-binding specificity. Single-molecule DNA curtain analysis provides insights into how BCDX2 enhances RAD51-ssDNA nucleoprotein filament assembly. Additionally, the cryogenic electron microscopy and functional analyses explain how RAD51C alterations found in patients with cancer inactivate DNA binding and the HR mediator activity of BCDX2.
Article
Multidisciplinary Sciences
Xizi Chen, Yilun Qi, Zihan Wu, Xinxin Wang, Jiabei Li, Dan Zhao, Haifeng Hou, Yan Li, Zishuo Yu, Weida Liu, Mo Wang, Yulei Ren, Ze Li, Huirong Yang, Yanhui Xu
Summary: This study elucidates the assembly mechanism of human TFIID-based PIC, showing two tracks for modular reorganization and direct promoter deposition, converging at a holo PIC with around 50 subunits. TFIID stabilizes PIC organization and supports CAK-mediated phosphorylation of Pol II.
Article
Multidisciplinary Sciences
Erik Zupa, Martin Wurtz, Annett Neuner, Thomas Hoffmann, Mandy Rettel, Anna Boehler, Bram J. A. Vermeulen, Sebastian Eustermann, Elmar Schiebel, Stefan Pfeffer
Summary: This study elucidates the molecular architecture and conformational plasticity of the augmin complex, providing insights into its role in branched microtubule formation and advancing our understanding of spindle formation in mitosis.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Lucas M. P. Chataigner, Christos Gogou, Maurits A. den Boer, Catia P. Frias, Dominique M. E. Thies-Weesie, Joke C. M. Granneman, Albert J. R. Heck, Dimphna H. Meijer, Bert J. C. Janssen
Summary: Cell-surface expressed contactin 1 and neurofascin 155 play important roles in controlling wiring of the nervous system. The crystallographic structures of the binding regions of contactin 1 and neurofascin 155 provide insights into the diverse adhesion sites formed through competing and complementary interfaces, post-translational glycosylation, splice differences, and structural plasticity. The structures also explain how these proteins enable the formation of specific intercellular distances and bridging of larger distances in the synapse.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Zhuangfeng Weng, Jiefu Zheng, Yiyi Zhou, Zuer Lu, Yixi Wu, Dongyi Xu, Huanhuan Li, Huanhuan Liang, Yingfang Liu
Summary: This study reports the structural characterization of the MCM8/9 complex using cryo-electron microscopy. The complex is arranged as a heterohexamer with a central channel for DNA binding. The N-terminal OB domains of MCM8/9 have hairpin structures that unwind duplex DNA. Activation by HROB leads to a change in symmetry and rotational motion of the C-tier ring, which is important for the unwinding ability of MCM8/9.
Article
Cell Biology
Ryoji Suno, Yukihiko Sugita, Kazushi Morimoto, Hiroko Takazaki, Hirokazu Tsujimoto, Mika Hirose, Chiyo Suno-Ikeda, Norimichi Nomura, Tomoya Hino, Asuka Inoue, Kenji Iwasaki, Takayuki Kato, So Iwata, Takuya Kobayashi
Summary: Prostaglandin receptors play important roles in inflammation, immune response, reproduction, and cancer. This study presents the structure of the human EP3-G(i) signaling complex using single-particle cryo-EM and compares it with other subtypes of prostaglandin receptors.
Article
Multidisciplinary Sciences
Tian Xie, Guangjun Xu, Yun Liu, Bradley Quade, Weichun Lin, Xiao-chen Bai
Summary: MuSK is a receptor tyrosine kinase that is essential for the neuromuscular junction. Its activation requires both agrin and LRP4 coreceptors. This study presents the cryo-EM structure of the extracellular ternary complex of agrin/LRP4/MuSK, revealing how LRP4 recruits agrin and MuSK to activate MuSK receptor.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Tian Xie, Guangjun Xu, Yun Liu, Bradley Quade, Weichun Lin, Xiao-chen Bai
Summary: MuSK is a receptor tyrosine kinase that plays a crucial role in the formation and maintenance of the neuromuscular junction. This study reveals the structure of the agrin/LRP4/MuSK ternary complex and uncovers the mechanism of how agrin and LRP4 coactivate the MuSK receptor.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cell Biology
Tian Tian, Lili Chen, Zhen Dou, Zhisen Yang, Xinjiao Gao, Xiao Yuan, Chengliang Wang, Ran Liu, Zuojun Shen, Ping Gui, Maikun Teng, Xianlei Meng, Donald L. Hill, Lin Li, Xuan Zhang, Xing Liu, Linfeng Sun, Jianye Zang, Xuebiao Yao
Summary: This study reveals the molecular basis of how human CCAN interacts with duplex DNA and its importance in accurate chromosome segregation through cryo-electron microscopy and functional analyses.
Article
Multidisciplinary Sciences
Yoko Fujita-Fujiharu, Yukihiko Sugita, Yuki Takamatsu, Kazuya Houri, Manabu Igarashi, Yukiko Muramoto, Masahiro Nakano, Yugo Tsunoda, Ichiro Taniguchi, Stephan Becker, Takeshi Noda
Summary: This study determines the structure of the Marburg virus nucleoprotein-RNA complex and provides mechanistic insight into the helical assembly of the nucleocapsid.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Frederik V. Schmidt, Luca Schulz, Jan Zarzycki, Simone Prinz, Niels N. Oehlmann, Tobias J. Erb, Johannes G. Rebelein
Summary: Nitrogenases are enzymes that can catalyze the reduction of dinitrogen to ammonia. Recent research has shown that nitrogenases can also reduce carbon dioxide and carbon monoxide to hydrocarbon compounds. In this study, the structure of the iron nitrogenase complex from Rhodobacter capsulatus was determined using cryogenic electron microscopy, revealing the presence of an [Fe8S9C-(R)-homocitrate] cluster in the active site. The study also highlighted differences in the interface between the two catalytic halves of the iron and molybdenum nitrogenases, which may influence the nitrogenase mechanism.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Yuyuan Zheng, Lei Ding, Xianhui Meng, Meg Potter, Alison L. Kearney, Jie Zhang, Jie Sun, David E. James, Guang Yang, Chun Zhou
Summary: Research has revealed that SIN1 is a vital component of mTORC2 and can interact with Ras family small GTPases through its Ras-binding domain (RBD). The association between Ras and SIN1/mTORC2 can potentially impact both mTORC2 and Ras-ERK pathways. By determining the high-resolution structures of HRas/KRas-SIN1 RBD complexes, researchers have identified the detailed interaction interface. Mutations in critical interface residues disrupt the Ras-SIN1 interaction, and in SIN1 knockout cells, it has been shown that the Ras-SIN1 association promotes SGK1 activity but inhibits insulin-induced ERK activation. Comparison with other Ras-binding proteins and experimental assays suggest that the association between HRas and SIN1 RBD is weaker than HRas-Raf1 RBD but slightly stronger than HRas-PI3K RBD, potentially explaining the different outcomes of insulin or EGF stimulation. Additionally, a Ras dimerization interface critical for Ras oligomerization has been uncovered. These findings contribute to our understanding of the Ras-SIN1 association and the cross-talk between growth factor-stimulated pathways.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Yan Zhang, Xiaoyun Pang, Jian Li, Jiashu Xu, Victor W. Hsu, Fei Sun
Summary: By using cryoelectron microscopy, researchers have revealed the protein lattice formed by SNX1, which helps to understand how it functions in generating transport carriers. Comparing the structure of SNX1 with that of an endosomal coat complex formed by retromer coupled to a SNX provides insights into the molecular organization of SNX and the intermediary stages of assembly leading to the formation of the complex on the membrane.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Huirong Yang, Zishuo Yu, Xizi Chen, Jiabei Li, Ningning Li, Jiaxuan Cheng, Ning Gao, Hai-Xin Yuan, Dan Ye, Kun-Liang Guan, Yanhui Xu
Summary: The Tuberous sclerosis complex (TSC) consists of TSC1, TSC2, and TBC1D7 in a 2:2:1 stoichiometry, forming an arch-shaped structure. The complex includes two TSC1 coiled-coils and one TBC1D7 bridging over the TSC2 dimer, showing asymmetry. The TSC2 GAP domains are symmetrically cradled within the core module formed by TSC2 dimerization domain and central coiled-coil of TSC1, revealing mechanisms of TSC complex assembly and GAP activity.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Kirstin Scherlach, Wolfgang Kuttenlochner, Daniel H. Scharf, Axel A. Brakhage, Christian Hertweck, Michael Groll, Eva M. Huber
Summary: This study reveals the mechanism by which the human pathogenic fungus Aspergillus fumigatus incorporates two sulfur atoms into its virulence factor through a specific GST GliG. The structures of GliG with glutathione and its reaction product shed light on the stepwise processing of Phe and Ser moieties in gliotoxin biosynthesis. Enzymatic C-S bond formation in gliotoxin and related natural compounds is further elucidated through activity assays with mutants.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Cell Biology
Heike Rampelt, Florian Wollweber, Mariya Licheva, Rinse de Boer, Inge Perschil, Liesa Steidle, Thomas Becker, Maria Bohnert, Ida van der Klei, Claudine Kraft, Martin van der Laan, Nikolaus Pfanner
Summary: Cristae, invaginations of the mitochondrial inner membrane, are important for oxidative phosphorylation. The study reveals that Mic10, a subunit of MICOS, also interacts with the F1Fo-ATP synthase, and it plays distinct roles in cristae shaping and respiratory adaptation and growth.
Article
Biochemical Research Methods
Mark Bates, Jan Keller-Findeisen, Adrian Przybylski, Andreas Hueper, Till Stephan, Peter Ilgen, Angel R. Cereceda Delgado, Elisa D'Este, Alexander Egner, Stefan Jakobs, Steffen J. Sahl, Stefan W. Hell
Summary: The dynamic model of the 4Pi point spread function allows for high three-dimensional resolution in localization microscopy. 4Pi-STORM imaging reveals nanoscale details of protein and nucleic acid organization in neurons and mitochondria. Despite challenges in instrumentation and data analysis, the development of a 4Pi-STORM microscope with dynamic PSF modeling and simpler optical design offers optimal resolution and accuracy for molecular organization studies.
Article
Biochemical Research Methods
Lynn M. Ostersehlt, Daniel C. Jans, Anna Wittek, Jan Keller-Findeisen, Kaushik Inamdar, Steffen J. Sahl, Stefan W. Hell, Stefan Jakobs
Summary: The combination of MINFLUX nanoscopy with DNA-PAINT labeling enables multi-color imaging of multiple molecular targets, leading to improved nanoscopy in fixed cells and increased multiplexing in MINFLUX imaging, as demonstrated by three-color imaging of mitochondria in mammalian cells.
Article
Multidisciplinary Sciences
Thiago Rodrigues-Oliveira, Florian Wollweber, Rafael I. Ponce-Toledo, Jingwei Xu, Simon K. -M. R. Rittmann, Andreas Klingl, Martin Pilhofer, Christa Schleper
Summary: Asgard archaea are close relatives of eukaryotes and their genomes contain hundreds of eukaryotic signature proteins (ESPs), which play a role in the formation of cytoskeleton and cellular structures. By studying a highly enriched culture of 'Candidatus Lokiarchaeum ossiferum', researchers found that this Asgard archaea has a larger genome and possesses a complex actin-based cytoskeleton, suggesting that such cytoskeleton existed prior to the emergence of eukaryotes.
Article
Multidisciplinary Sciences
Tianyan Liu, Till Stephan, Peng Chen, Jan Keller-Findeisen, Jingting Chen, Dietmar Riedel, Zhongtian Yang, Stefan Jakobs, Zhixing Chen
Summary: This study reports a mitochondrial inner membrane fluorescent marker, PK Mito Orange (PKMO), which features reduced phototoxicity and high stability, enabling super-resolution recordings of mitochondrial inner membrane dynamics. The PKMO dye is optically orthogonal with green and far-red markers, allowing multiplexed recordings. By using multi-color STED microscopy, interactions between mitochondria and other cellular components can be captured at sub-100 nm resolution.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Alexander von der Malsburg, Gracie M. Sapp, Kelly E. Zuccaro, Alexander von Appen, Frank R. Moss, Raghav Kalia, Jeremy A. Bennett, Luciano A. Abriata, Matteo Dal Peraro, Martin van der Laan, Adam Frost, Halil Aydin
Summary: This study reveals the molecular mechanisms of OPA1-dependent membrane remodeling and fusion, providing a structural framework for understanding how human OPA1 shapes mitochondrial morphology and showing how human disease mutations compromise OPA1 functions.
Correction
Biology
Vahid Ebrahimi, Till Stephan, Jiah Kim, Pablo Carravilla, Christian Eggeling, Stefan Jakobs, Kyu Young Han
COMMUNICATIONS BIOLOGY
(2023)
Article
Biology
Vahid Ebrahimi, Till Stephan, Jiah Kim, Pablo Carravilla, Christian Eggeling, Stefan Jakobs, Kyu Young Han
Summary: This study demonstrates that restoring STED microscopy images using deep learning can reduce the effects of photobleaching and photodamage by decreasing the pixel dwell time. Our method effectively and reliably restores noisy 2D and 3D STED images, enabling long-term observation of mitochondrial dynamics.
COMMUNICATIONS BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Dojin Kim, Stefan Stoldt, Michael Weber, Stefan Jakobs, Vladimir N. N. Belov, Stefan W. W. Hell
Summary: Disulfonated rhodamines, commonly used in life science and optical microscopy, were previously thought to be impermeable to living cells. This assumption was challenged by using five popular rhodamines combined with a HaloTag (TM) amine (O-2) ligand (x) to successfully label living cells. Three compounds with two negative charges, Rho590-x, Rho565-x, and Rho530-x, showed specific and bright staining in living cells and performed well in STED microscopy. Other probes with one negative charge, prepared by native chemical ligation and esterification, exhibited specific staining and red shifts in absorption and emission bands.
