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
Multidisciplinary Sciences
Tobias Bock-Bierbaum, Kathrin Funck, Florian Wollweber, Elisa Lisicki, Karina von der Malsburg, Alexander von der Malsburg, Janina Laborenz, Jeffrey K. Noel, Manuel Hessenberger, Sibylle Jungbluth, Carola Bernert, Severine Kunz, Dietmar Riedel, Hauke Lilie, Stefan Jakobs, Martin van der Laan, Oliver Daumke
Summary: Mitochondrial cristae membranes are where oxidative phosphorylation occurs in cells, and cristae junctions serve as selective entry gates into the cristae space. The Mic60-Mic19 subcomplex acts as a molecular strut, controlling the architecture and function of cristae junctions.
Article
Biochemistry & Molecular Biology
Cheuk Hei Ho, Chiara Paolantoni, Praveen Bawankar, Zuojian Tang, Stuart Brown, Jean-Yves Roignant, Jessica E. Treisman
Summary: The exon junction complex regulates various functions related to mRNA splicing, translation, degradation, and localization, with Barentsz playing a distinct role in Drosophila neuromuscular development. Barentsz is involved in mitochondrial distribution and synapse growth, independent of its interactions with the exon junction complex. Additionally, Barentsz influences synapse growth through the regulation of Activin ligand Dawdle expression.
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
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
Biochemistry & Molecular Biology
V. M. Datta Darshan, Venketesh Sivaramakrishnan, K. Arvind Kumar
Summary: This study aims to investigate the effects of missense and nonsense SNPs on protein degradation and functional consequences. Computational tools and models are used to analyze the impact of these SNPs on protein-protein interactions and functional networks.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
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
Multidisciplinary Sciences
Yishuo Lu, Peng Zuo, Hongyi Chen, Hui Shan, Weize Wang, Zonglin Dai, He Xu, Yayu Chen, Ling Liang, Dian Ding, Yan Jin, Yuxin Yin
Summary: In this study, the cryo-EM structures of BTR1 in the outward-facing state and inward-facing state were determined, revealing the binding of the activating ligand PIP2 at the interface between the transmembrane domain and the N-terminal cytosolic domain of BTR1. Disruption of the PIP2 binding site or protonation of PIP2 phosphate groups by acidic pH can convert BTR1 into the inward-facing conformation.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Yishuo Lu, Peng Zuo, Hongyi Chen, Hui Shan, Weize Wang, Zonglin Dai, He Xu, Yayu Chen, Ling Liang, Dian Ding, Yan Jin, Yuxin Yin
Summary: This study presents the structures of human BTR1 and provides insights into the mechanisms of activation by the ligand PIP2 and the effects of pathogenic mutations on its conformation and transport activity.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Nadia Sukusu Nielsen, Trine A. F. Gadeberg, Ebbe Toftgaard Poulsen, Seandean Lykke Harwood, Christian E. Weberskov, Jan Skov Pedersen, Gregers R. Andersen, Jan J. Enghild
Summary: Mutations in the extracellular matrix protein TGFBIp are associated with protein aggregation in the cornea, leading to vision problems. Crystal structure analysis revealed new dimer interfaces in the mutants R124H and R555W, potentially central to their aggregation mechanism. Solution studies showed interactions between wildtype and mutant TGFBIps, suggesting new therapeutic opportunities for treating corneal dystrophy.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Katharina Braunger, Jiyoon Ahn, Matthijs M. Jore, Steven Johnson, Terence T. L. Tang, Dennis V. Pedersen, Gregers R. Andersen, Susan M. Lea
Summary: The authors report the identification and characterisation of a species-specific properdin inhibitor CirpA derived from tick saliva, opening avenues for future therapeutic approaches.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Heidi Gytz Olesen, Iliana Michailidou, Wioleta M. Zelek, Jeroen Vreijling, Patrick Ruizendaal, Ferry de Klein, J. Arnoud Marquart, Thomas B. Kuipers, Hailiang Mei, Yuchun Zhang, Muhammad Ahasan, Krista K. Johnson, Yi Wang, B. Paul Morgan, Marcus van Dijk, Kees Fluiter, Gregers Rom Andersen, Frank Baas
Summary: Damage and disease of nerves activate the complement system, leading to the formation of the membrane attack complex (MAC) and delaying nerve regeneration. By studying the complement component C6, researchers have developed a novel therapeutic monoclonal antibody, CP010, that prevents MAC formation and shows potential therapeutic use in neurological diseases. The antibody blocks the interaction between C6 and C5/C5b and demonstrates efficacy in preventing disease and relapse in animal models.
JOURNAL OF INNATE IMMUNITY
(2023)
Article
Multidisciplinary Sciences
Nadia Sukusu Nielsen, Alessandra Zarantonello, Seandean Lykke Harwood, Kathrine Tejlgard Jensen, Katarzyna Kjoge, Ida B. Thogersen, Leif Schauser, Jesper Lykkegaard Karlsen, Gregers R. Andersen, Jan J. Enghild
Summary: This study investigates the protease-inhibitory mechanism of human A2ML1 and determines the structures of its native and protease-cleaved conformations. The functional unit of A2ML1 is a monomer that depends on covalent binding of the protease to achieve inhibition. Structural analysis shows that disruption of the bait region triggers conformational changes, resulting in protease inhibition.
NATURE COMMUNICATIONS
(2022)
Article
Allergy
Melanie Plum, Luna Tjerrild, Tim Raiber, Frank Bantleon, Sara Bantleon, Michaela Miehe, Frederic Jabs, Henning Seismann, Christian Moebs, Wolfgang Pfutzner, Thilo Jakob, Gregers R. Andersen, Edzard Spillner
Summary: This study provides evidence for the relevance of N-glycan recognition in T(H)2 responses and suggests that IgE and IgG antibodies to ubiquitous carbohydrate epitopes can be equivalent to those directed against proteinaceous epitopes with clinical implications.
Article
Biochemistry & Molecular Biology
Rasmus K. Jensen, Henrik Pedersen, Josefine Lorentzen, Nick Stub Laursen, Thomas Vorup-Jensen, Gregers Rom Andersen
Summary: This study reveals the mechanism of α(M)β(2) integrin receptor binding to ligand and presents the atomic structure of the human α(M)β(2) headpiece fragment complexed with the nanobody hCD11bNb1. It is found that the nanobody acts as a competitive inhibitor by sterically hindering the binding of complement component iC3b to the α(M) subunit. Surprisingly, the nanobody also stimulates the interaction between α(M)β(2) and iC3b.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Maiken Lumby Henriksen, Christian Nielsen, Dennis Pedersen, Gregers Rom Andersen, Steffen Thiel, Yaseelan Palarasah, Soren Werner Karlskov Hansen
Summary: Factor D is a serine protease involved in immune responses and antibody functions. The mature form of factor D is the most abundant in circulation, while the pro-form accounts for 8-15% of total factor D. Blood sampling procedures can affect conversion and measurement levels.
JOURNAL OF IMMUNOLOGICAL METHODS
(2022)
Letter
Multidisciplinary Sciences
Seandean Lykke Harwood, Gregers Rom Andersen, Jan J. Enghild
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Henrik Pedersen, Rasmus Kjeldsen Jensen, Annette Gudmann Hansen, Steen Vang Petersen, Steffen Thiel, Nick Stub Laursen, Gregers Rom Andersen
Summary: The complement system plays a role in labeling pathogens and dying host cells for clearance. A nanobody has been discovered that specifically binds to degradation products of complement component C3 and effectively inhibits complement deposition. This nanobody could be a potential candidate for studying complement-related diseases in rodent models.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Vivien R. Schack, Morten K. Herlin, Henrik Pedersen, J. Magnus Bernth Jensen, Mia Faerch, Bettina Bundgaard, Rasmus K. Jensen, Uffe B. Jensen, Rikke Christensen, Gregers R. Andersen, Steffen Thiel, Per Hollsberg
Summary: We report a pediatric patient with aHUS carrying a previously unreported homozygous variant in CD46. Functional analyses showed that this variant caused complement dysregulation through multiple mechanisms. These findings highlight the coexistence of multiple mechanisms that may disrupt CD46 function during aHUS development.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Review
Immunology
Dennis Vestergaard Pedersen, Josefine Lorentzen, Gregers Rom Andersen
Summary: This article reviews the recent progress in the structure determination of alternative pathway protein FP, highlighting the regions involved in the interactions between C3b, factor B, and FP. The study also sheds light on the relationship between FP activity and its oligomerization state, and discusses the structural basis for FP deficiency and tick-mediated inhibition. Overall, the accumulated structural knowledge provides a comprehensive basis for understanding molecular interactions involving FP and its role in various pathological conditions.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Biochemistry & Molecular Biology
Josefine Lorentzen, Dennis Vestergaard Pedersen, Trine Amalie Fogh Gadeberg, Gregers Rom Andersen
Summary: This study presents a method to stabilize unstable macromolecular complexes by linking subunits through nanobodies, and successfully determines the crystal structure of a 320 kDa proconvertase. The results highlight the role of noncanonical loops in properdin protein in enhancing the activity of the C3 convertase.
Editorial Material
Hematology
Gregers Rom Andersen
Summary: In this study, Andersen et al1 provide a detailed structural characterization of lufaxin, a 32-kDa protein found in the saliva of the blood-feeding sand fly Lutzomyia longipalpis. They demonstrate that lufaxin can form a large complex with a complement proconvertase and the coagulation factor fXa, leading to the inhibition of complement C3 proconvertase activation and fXa proteolytic activity.
Article
Engineering, Environmental
Yan Zhang, Thea Jess Plesner, Yi Ouyang, Yu-Cong Zheng, Etienne Bouhier, Emilie Ingemann Berentzen, Mingliang Zhang, Pengfei Zhou, Wolfgang Zimmermann, Gregers Rom Andersen, Bekir Engin Eser, Zheng Guo
Summary: A novel thermophilic laccase, LfLAC3, was identified from PE-degrading Lysinibaccillus fusiformis through computer-aided and activity-based screening. LfLAC3 showed high robustness and catalytic promiscuity. It was able to degrade all tested dyes and low-density polyethylene films without the use of a mediator, indicating its potential for dye decolorization and plastic degradation.
JOURNAL OF HAZARDOUS MATERIALS
(2023)
Article
Chemistry, Multidisciplinary
Dante Guldbrandsen Andersen, Andreas Botker Pedersen, Martin Hogholm Jorgensen, Mireia Casanovas Montasell, Ane Bretschneider Sogaard, Gal Chen, Avi Schroeder, Gregers Rom Andersen, Alexander N. Zelikin
Summary: In this study, synthetic cells with an artificial signaling pathway connecting an extracellular trigger event to the activation of intracellular transcription are engineered. The results highlight the importance of cellularity and demonstrate a significant step towards the design of synthetic cells with responsive behavior, moving towards life-like cell mimics.
ADVANCED MATERIALS
(2023)