Article
Biochemistry & Molecular Biology
Aaron M. N. Joiner, Ben P. Phillips, Kumar Yugandhar, Ethan J. Sanford, Marcus B. Smolka, Haiyuan Yu, Elizabeth A. Miller, J. Christopher Fromme
Summary: The study revealed the regulation of Rab1 activation by the TRAPPIII complex, with the Trs85 subunit serving as a membrane anchor for the entire complex via its amphipathic helix. These findings provide a structural understanding of Rab activation on organelle and vesicle membranes.
Review
Urology & Nephrology
Jun Matsuda, Kana Asano-Matsuda, Thomas M. Kitzler, Tomoko Takano
Summary: Rho GTPases play a crucial role in regulating the actin cytoskeleton and are implicated in the pathogenesis of proteinuric glomerular diseases. These GTPases are primarily regulated by three families of proteins – GEFs, GAPs, and GDIs – with their upstream regulatory mechanisms largely unknown in podocytes. Further studies are needed to bridge the knowledge gap in the field.
KIDNEY INTERNATIONAL
(2021)
Article
Biology
Yasmin ElMaghloob, Begona Sot, Michael J. McIlwraith, Esther Garcia, Tamas Yelland, Shehab Ismail
Summary: The study demonstrates that BART acts as a bona fide co-GEF for ARL3, interacting with ARL3 and ARL13B to efficiently activate ARL3 and maintain its active state. This finding contributes to a better understanding of the role of ARL3 in regulating ciliary function.
Article
Multidisciplinary Sciences
Xin Yong, Guowen Jia, Zhe Liu, Chunzhuang Zhou, Jiamin Yi, Li Chen, Lu Chen, Yuan Wang, Qingxiang Sun, Daniel D. Billadeau, Zhaoming Su, Da Jia
Summary: In this study, the structure of the Drosophila Mon1-Ccz1-RMC1 complex was determined using cryogenic-electron microscopy. RMC1 acts as a scaffolding subunit and binds to both Mon1 and Ccz1, explaining the binding specificity of the complex. The assembly of RMC1 with Mon1-Ccz1 is required for cellular RAB7A activation, autophagic functions, and organismal development in zebrafish.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Dennis Quentin, Jan S. Schuhmacher, Bjoern U. Klinkh, Jeni Lauer, Tanvir R. Shaikh, Pim J. Huis in 't Veld, Luisa M. Welp, Henning Urlaub, Marino Zerial, Stefan Raunser
Summary: This study determines the cryo-EM structure of human FERRY, which has a unique clamp-like architecture distinct from other Rab effectors. Functional and mutational studies reveal that the C-terminal coiled-coil of Fy-2 acts as the binding region for Fy-1/3 and Rab5, while both coiled-coils and Fy-5 are involved in mRNA binding. Mutations causing truncations of Fy-2 in patients with neurological disorders impair Rab5 binding or FERRY complex assembly. Fy-2 serves as a binding hub that connects all five complex subunits and mediates the binding to mRNA and early endosomes via Rab5. The study provides mechanistic insights into long-distance mRNA transport and introduces a new mode of RNA binding involving coiled-coil domains.
Article
Biochemistry & Molecular Biology
Susobhan Mahanty, Krishnan Rathinasamy
Summary: The natural anthraquinone purpurin was found to effectively inhibit bacterial cell growth by perturbing FtsZ assembly and inducing bacterial cell filamentation. It also inhibited proliferation of mammalian cancer cells without disrupting tubulin polymerization. These findings suggest that purpurin could serve as a lead molecule for the development of antibacterial agents.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Saket R. Bagde, J. Christopher Fromme
Summary: Correct localization of Rab GTPases in cells is crucial for membrane trafficking. GEFs, such as TRAPP complexes TRAPPII and TRAPPIII, activate specific Rabs on organelle and vesicle membranes. The length of Rab C-terminal hypervariable domain (HVD) plays a critical role in substrate selection. Cryo-EM studies have provided insights into how TRAPP complexes identify and activate their substrates.
Article
Biochemistry & Molecular Biology
Mingxing Wang, Huan Feng, Peng Xu, Qiujin Xie, Jinpeng Gao, Yanzhang Wang, Xiaowei Zhang, Jun Yang, Jeremy D. Murray, Fengli Sun, Chunyan Wang, Ertao Wang, Nan Yu
Summary: The study identified the crucial roles of small GTPases and Nod factor receptor in root hair development and infection process in Medicago truncatula, regulating polar growth and deformation of root hairs through activation and interaction mechanisms.
JOURNAL OF INTEGRATIVE PLANT BIOLOGY
(2021)
Article
Plant Sciences
Xiaojiao Xiang, Shuzhan Zhang, En Li, Xue-Lian Shi, Jing-Yu Zhi, Xin Liang, Gui-Min Yin, Zheng Qin, Sha Li, Yan Zhang
Summary: Pollen germination is a process of polarity establishment, and ROPs play a critical role in this process. In addition, BDR8 and BDR9 are identified as ROP effectors in pollen germination.
Article
Multidisciplinary Sciences
Hui Tu, Zhimeng Wang, Ye Yuan, Xilin Miao, Dong Li, Hu Guo, Yihong Yang, Huaqing Cai
Summary: The study identifies a complex composed of two proteins, PripA and TbcrA, that plays a central role in the conversion of Rab5 to Rab7 during macropinosome maturation, facilitating efficient cargo trafficking.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Alya Hussain, Vu T. Nguyen, Philip Reigan, Michael McMurray
Summary: The primary function of nucleotide binding and hydrolysis by septins is to ensure formation of G interfaces that impose the proper subunit-subunit order within the hetero-oligomer. Evolutionary changes in the septin G interface have occurred in yeast and nematodes to accommodate variations in nucleotide occupancy.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Aaron M. N. Joiner, J. Christopher Fromme
Summary: This study provides insights into the initiation of the eukaryotic secretory pathway, focusing on the interaction between Sar1 and Sec12 in cargo protein packaging and membrane insertion mechanisms.
Article
Cell Biology
Lisheng Fu, Xiaoyan Wang, Ying Yang, MeiHua Chen, Adilijiang Kuerban, Haojie Liu, Yiwei Dong, QianQian Cai, Mingzhe Ma, XingZhong Wu
Summary: SEPT11 plays a crucial role in hepatocellular carcinoma (HCC) by promoting metastasis and regulating cytoskeleton rearrangement. It is highly expressed in various tumors, including HCC, and associated with poor prognosis. SEPT11 acts as an oncogene in HCC and could be a potential therapeutic target.
CELL DEATH & DISEASE
(2023)
Article
Cell Biology
Shu Hiragi, Takahide Matsui, Yuriko Sakamaki, Mitsunori Fukuda
Summary: Hiragi et al. identify TBC1D18 as a Rab5-GAP associated with Mon1 that mediates endosome maturation. They propose a new model where Mon1-Ccz1 and TBC1D18 coordinate endosome maturation by inactivating Rab5 and activating Rab7. The study demonstrates that defects in endosome maturation are primarily caused by Rab5 hyperactivation rather than Rab7 inactivation.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Cell Biology
Shuangjiang Li, Martina Cerri, Pamela Strazzer, Yanbang Li, Cornelis Spelt, Mattijs Bliek, Michiel Vandenbussche, Enric Martinez-Calvo, Biao Lai, Lara Reale, Ronald Koes, Francesca M. Quattrocchio
Summary: The study demonstrates that RAB5a protein in plants regulates trafficking to the central vacuole, with evolutionarily and functionally distinct features from other types of RAB5 proteins. Loss of RAB5a reduces cell height and abolishes vacuolino formation, while overexpression of RAB5a promotes vacuolino fusion, resulting in oversized vacuoles.
Article
Multidisciplinary Sciences
Raimond B. G. Ravelli, Frank J. T. Nijpels, Rene J. M. Henderikx, Giulia Weissenberger, Sanne Thewessem, Abril Gijsbers, Bart W. A. M. M. Beulen, Carmen Lopez-Iglesias, Peter J. Peters
NATURE COMMUNICATIONS
(2020)
Article
Biochemistry & Molecular Biology
Christine Roeder, Tatsiana Kupreichyk, Lothar Gremer, Luisa U. Schaefer, Karunakar R. Pothula, Raimond B. G. Ravelli, Dieter Willbold, Wolfgang Hoyer, Gunnar F. Schroeder
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Mart M. Lamers, Jelte van der Vaart, Kevin Knoops, Samra Riesebosch, Tim Breugem, Anna Z. Mykytyn, Joep Beumer, Debby Schipper, Karel Bezstarosti, Charlotte D. Koopman, Nathalie Groen, Raimond B. G. Ravelli, Hans Q. Duimel, Jeroen A. A. Demmers, Georges M. G. M. Verjans, Marion P. G. Koopmans, Mauro J. Muraro, Peter J. Peters, Hans Clevers, Bart L. Haagmans
Summary: This study describes a human 2D air-liquid interface culture system for studying interactions between SARS-CoV-2 and host cells, showing potential as an experimental model and drug screening tool. The system is characterized by the infection of alveolar cells and induction of interferon response, with interferon lambda 1 treatment reducing viral replication.
Article
Crystallography
Abril Gijsbers, Nuria Sanchez-Puig, Ye Gao, Peter J. Peters, Raimond B. G. Ravelli, Dritan Siliqi
Summary: Tuberculosis has been a global burden for centuries, with gaps in our understanding of its pathogenesis hindering the development of new treatments. The ESX-1 machinery is responsible for secreting virulence factors that manipulate the host response, with the protein EspK playing a crucial role in this process. Structural studies have revealed the unique architecture of the EspK protein, highlighting its importance in the pathogenicity of tuberculosis.
Article
Cell Biology
Rie Ayukawa, Seigo Iwata, Hiroshi Imai, Shinji Kamimura, Masahito Hayashi, Kien Xuan Ngo, Itsushi Minoura, Seiichi Uchimura, Tsukasa Makino, Mikako Shirouzu, Hideki Shigematsu, Ken Sekimoto, Benoit Gigant, Etsuko Muto
Summary: This study demonstrates that the formation of straight oligomers of critical size is essential for nucleation of microtubules. Both GDP and GTP tubulin form single-stranded oligomers with different curvature distributions, and the proportion of straight oligomers can accelerate nucleation. The results suggest that cellular factors involved in nucleation promote it via stabilization of straight oligomers.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Casper Berger, Raimond B. G. Ravelli, Carmen Lopez-Iglesias, Peter J. Peters
Summary: Cryo-electron tomography on FIB-milled lamellae is a powerful technique for determining the structure of macromolecular complexes in their native cellular environment. A simple method was described to allow uptake of BSA-gold fiducials into mammalian cells, which improved the alignment of tilt-series. This technique can contribute to understanding cells at a structural and ultrastructural level with both cryo- and room-temperature electron tomography, and has the potential to be used for correlative light and electron microscopy studies.
JOURNAL OF STRUCTURAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Casper Berger, Raimond B. G. Ravelli, Carmen Lopez-Iglesias, Mikhail Kudryashev, Andreas Diepold, Peter J. Peters
Summary: Researchers visualized the structure of Yersinia enterocolitica injectisomes inside infected human myeloid cells using cryo-electron microscopy techniques. They found that a minimum needle length is required for injectisomes to contact host membranes and observed some injectisomes causing bending of host membranes.
JOURNAL OF STRUCTURAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Paloma F. Varela, Melanie Chenon, Christophe Velours, Kristen J. Verhey, Julie Menetrey, Benoit Gigant
Summary: Motile kinesins are motor proteins that move along microtubules by hydrolyzing ATP. This study provides structural insights into the nucleotide cycle of OSM-3, demonstrating a shared ATPase mechanism similar to that of Eg5 in the kinesin superfamily.
Article
Biochemical Research Methods
Abril Gijsbers, Yue Zhang, Ye Gao, Peter J. Peters, Raimond B. G. Ravelli
Summary: This study presents a straightforward method for expressing and purifying bacterioferritin B (BfrB) from Mycobacterium tuberculosis with high yield and purity. The 2.12 angstrom resolution cryo-EM structure of BfrB reveals a unique C-terminal extension that provides additional stability to the protein. These findings and protocol could benefit the growing cryo-EM community in characterizing and pushing the limits of their electron microscopes and workflows.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2021)
Article
Instruments & Instrumentation
Yue Zhang, Peng-Han Lu, Enzo Rotunno, Filippo Troiani, J. Paul van Schayck, Amir H. Tavabi, Rafal E. Dunin-Borkowski, Vincenzo Grillo, Peter J. Peters, Raimond B. G. Ravelli
Summary: Imaging biomolecules with ionizing radiation like electrons causes radiation damage, limiting the number of high-energy electrons available for imaging and resulting in low signal-to-noise ratios. Radiation damage alters molecular structures and dampens high-resolution details from the microscope and detector's transfer functions. Traditional electron microscopy is restricted by radiation damage in handling particle size and sample heterogeneity.
JOURNAL OF SYNCHROTRON RADIATION
(2021)
Article
Biochemistry & Molecular Biology
Nino Iakobachvili, Stephen Adonai Leon-Icaza, Kevin Knoops, Norman Sachs, Serge Mazeres, Roxane Simeone, Antonio Peixoto, Celia Bernard, Marlene Murris-Espin, Julien Mazieres, Kaymeuang Cam, Christian Chalut, Christophe Guilhot, Carmen Lopez-Iglesias, Raimond B. G. Ravelli, Olivier Neyrolles, Etienne Meunier, Geanncarlo Lugo-Villarino, Hans Clevers, Celine Cougoule, Peter J. Peters
Summary: The study found that Mycobacterium tuberculosis and Mycobacterium abscessus mainly exist as extracellular bacteria in human airway organoids, infecting epithelial cells with low efficiency. The organoids respond to infection by modulating cytokine, antimicrobial peptide, and mucin gene expression. Adult stem cell-derived airway organoids can be used to elucidate early events of mycobacterial infection in human settings.
MOLECULAR MICROBIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Andreas Stein, Persefoni Hilken Nee Thomopoulou, Corazon Frias, Sina M. Hopff, Paloma Varela, Nicola Wilke, Arul Mariappan, Jorg-Martin Neudoerfl, Alexey Yu Fedorov, Jay Gopalakrishnan, Benoit Gigant, Aram Prokop, Hans-Gunther Schmalz
Summary: The synthesis and investigation of PT-100, a potential anticancer drug, were reported. PT-100 exhibited high antiproliferative and apoptosis-inducing effects, especially in multidrug-resistant cancer cell lines, and showed synergistic effects with vincristine in certain cell lines.
Article
Multidisciplinary Sciences
Valerie Campanacci, Agathe Urvoas, Liza Ammar Khodja, Magali Aumont-Nicaise, Magali Noiray, Sylvie Lachkar, Patrick A. Curmi, Philippe Minard, Benoit Gigant
Summary: The study demonstrates the binding of CPAP's PN2-3 domain with tubulin and the similarity in binding mode with fungal and bacterial inhibitors. This finding uncovers the characteristic features of cellular partners binding to this site and highlights the structural convergence of CPAP with small-molecule inhibitors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Abril Gijsbers, Mathias Eymery, Ye Gao, Isabella Menart, Vanesa Vinciauskaite, Dritan Siliqi, Peter J. Peters, Andrew McCarthy, Raimond B. G. Ravelli
Summary: Pathogenic species from the Mycobacterium genus use specialized secretion systems (ESX-1 to ESX-5) to transport virulence factors across their cell envelope, influencing immune response and cell death. This study presents the crystal structure of Mycobacterium tuberculosis ESX-1 secretion-associated substrate EspB bound to its chaperone EspK, revealing a mechanism for the secretion of EspB in Mycobacterium species.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Abril Gijsbers, Vanesa Vinciauskaite, Axel Siroy, Ye Gao, Giancarlo Tria, Anjusha Mathew, Nuria Sanchez-Puig, Carmen Lopez-Iglesias, Peter J. Peters, Raimond B. G. Ravelli
Summary: ESX-1 is a crucial virulence factor of Mycobacterium tuberculosis, involved in disrupting the phagosome membrane of host cells to evade immune system defence. The study reveals the oligomerization process of ESX-1 substrate EspB and suggests its potential role as a structural element of ESX-1. Cryo-electron microscopy data shows conservation of EspB quaternary structure across slow growing species but not in fast growing M. smegmatis.
CURRENT RESEARCH IN STRUCTURAL BIOLOGY
(2021)