Article
Multidisciplinary Sciences
Dennis M. Mwangangi, Edward Manser, Robert C. Robinson
Summary: The mechanism by which twinfilin uncaps actin filaments involves inducing a conformational change in G-actin and disrupting critical actin-capping protein interactions. Twinfilin plays an essential role in promoting filament uncapping by interfering with the stable capping of actin filaments.
Article
Cell Biology
Jocelyn F. Krey, Chang Liu, Inna A. Belyantseva, Michael Bateschell, Rachel A. Dumont, Jennifer Goldsmith, Paroma Chatterjee, Rachel S. Morrill, Lev M. Fedorov, Sarah Foster, Jinkyung Kim, Alfred L. Nuttall, Sherri M. Jones, Dongseok Choi, Thomas B. Friedman, Anthony J. Ricci, Bo Zhao, Peter G. Barr-Gillespie
Summary: The stereocilia rootlet plays a critical role in protecting vertebrate hair cells from overstimulation. This study demonstrates that the ANKRD24 protein concentrates at the insertion point of the stereocilia, forming a ring and binding with TRIOBP-5 to maintain its distribution. ANKRD24 and TRIOBP-5 together organize the rootlets, enabling long-term auditory resilience.
JOURNAL OF CELL BIOLOGY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Timothy L. Cover
Summary: A split luciferase assay was developed to monitor the T4SS-mediated translocation of CagA into host cells in real-time, facilitating the quantitative analysis of CagA translocation and the kinetics of its delivery. This system also confirmed the importance of protein unfolding for secretion by the Cag T4SS.
MOLECULAR MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ingrid Richter, Philipp Wein, Zerrin Uzum, Claire E. Stanley, Jana Krabbe, Evelyn M. Molloy, Nadine Moebius, Iuliia Ferling, Falk Hillmann, Christian Hertweck
Summary: As a symbiotic partner of the fungus Rhizopus microsporus, the bacterium Mycetohabitans rhizoxinica faces challenges in evading the host's defense mechanisms. The role of a transcription activator-like (TAL) effector released by the endobacteria as an essential symbiosis factor has been discovered.
Article
Multidisciplinary Sciences
Takayuki Yasunaga, Johannes Wiegel, Max D. Bergen, Martin Helmstaedter, Daniel Epting, Andrea Paolini, Oezgun Cicek, Gerald Radziwill, Christina Engel, Thomas Brox, Olaf Ronneberger, Peter Walentek, Maximilian H. Ulbrich, Gerd Walz
Summary: Motile cilia of Xenopus epidermis are anchored to microridge-like membrane protrusions to maintain their directionality. The actin cytoskeleton is dynamic during the early development of multiciliated cells, and subapical actin filaments are anchored to microridge-like structures. These observations identify microridge-like structures as an essential component of basal body rootlet anchoring in MCCs.
NATURE COMMUNICATIONS
(2022)
Article
Mechanics
Pascal Mindermann, Marta Gil Perez, Naoki Kamimura, Jan Knippers, Goetz T. Gresser
Summary: Fiber-reinforced composite structures manufactured by coreless filament winding (CFW) offer high mechanical performance in specific load cases. This study utilizes an integrated fiber optical sensor operating by the Rayleigh backscatter principle to improve the understanding of structural behavior and reduce safety factors. The sensor system provides high spatial resolution to measure and analyze strain fields in different load scenarios, allowing for the iterative derivation of actual load introduction.
COMPOSITE STRUCTURES
(2022)
Article
Biochemistry & Molecular Biology
Kuo Zhang, Ting Peng, Xinyuan Tao, Miao Tian, Yanxin Li, Zhao Wang, Shuaifei Ma, Shufan Hu, Xing Pan, Juan Xue, Jiwei Luo, Qiulan Wu, Yang Fu, Shan Li
Summary: This study reveals the multistep enzymatic mechanism of CopC-catalyzed arginine ADPR deacylization in resisting bacterial infections, providing a structural framework for understanding the molecular basis of this process.
Review
Plant Sciences
Yihao Li, Xin Zhang, Yi Zhang, Haiyun Ren
Summary: This review focuses on the organization and dynamics of actin filaments and microtubule network in guard cells during stomatal movement. The role of cytoskeletal-associated proteins in cytoskeletal rearrangements during stomatal movement is also discussed. The potential mechanisms of stomatal movement in relation to the cytoskeleton are explored, providing a foundation for further research in this field.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Multidisciplinary Sciences
Selen Manioglu, Seyed Majed Modaresi, Noah Ritzmann, Johannes Thoma, Sarah A. Overall, Alexander Harms, Gregory Upert, Anatol Luther, Alexander B. Barnes, Daniel Obrecht, Daniel J. Muller, Sebastian Hiller
Summary: The study uses high-resolution atomic force microscopy to investigate the interaction mechanism between Polymyxins and bacterial membranes. The results show that Polymyxins can arrange bacterial lipids into regular hexagonal structures, making the membrane stiffer and leading to rupture.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Damian Lobato-Marquez, Jingwei Xu, Gizem Oezbaykal Gueler, Adaobi Ojiakor, Martin Pilhofer, Serge Mostowy
Summary: Septins are cytoskeletal proteins that form cage-like structures to restrict the movement of bacteria within cells. Research shows that septin complexes can recognize bacterial cells and assemble as filaments on their surface.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Yasuhide Kuwabara, Allen J. York, Suh-Chin Lin, Michelle A. Sargent, Kelly M. Grimes, James P. Pirruccello, Jeffery D. Molkentin
Summary: We identified a variant in the FLII gene that is associated with cardiac remodeling in heart disease. Further studies showed that Flii protein binds to sarcomeric actin thin filament and affects its length. Deletion of Flii or introduction of the R1245H amino acid substitution in mice resulted in cardiomyopathy due to shortening of actin thin filaments. The FLII variant increases the risk of cardiomyopathy by altering sarcomere structure and contractile dynamics.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Yoshihiro Ueda, Koichiro Higasa, Yuji Kamioka, Naoyuki Kondo, Shunsuke Horitani, Yoshiki Ikeda, Wolfgang Bergmeier, Yoshinori Fukui, Tatsuo Kinashi
Summary: Lymphocyte trafficking requires precise regulation of chemokine-mediated cell migration, which depends on cytoskeletal dynamics and polarity. This study reveals that the integrin activator Rap1 plays critical roles in lymphocyte polarization and chemotaxis independent of adhesion. Rap1 activation involves F-actin scaffolds, stimulates RhoA activation and actomyosin contractility at the rear, and requires the downstream effector talin1 for actomyosin contractility in the uropod. These findings provide insights into the regulatory mechanisms of lymphocyte trafficking.
Article
Immunology
George F. Aranjuez, Jongeon Kim, Travis J. Jewett
Summary: In this study, the interaction between the Chlamydia trachomatis effector Tarp and F-actin was studied using a transgenic Drosophila melanogaster model. Results showed that Tarp expression disrupted F-actin dynamics during bristle development and competed with the host bundler Singed/Fascin. Additionally, Tarp partially rescued the morphological defects caused by the loss of the singed gene.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Szilard Szikora, Peter Gorog, Jozsef Mihaly
Summary: Actin-containing tropomyosin and troponin decorated thin filaments are crucial components of the contractile apparatus in muscles. The optimal length of these filaments is critical for efficient muscle activity and can be regulated by various mechanisms. Mutations affecting these factors can alter thin filament length and are associated with certain diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Peter J. Carman, Kyle R. Barrie, Grzegorz Rebowski, Roberto Dominguez
Summary: This study describes the structures of the free and capped ends of F-actin using cryo-electron microscopy. The terminal subunits at the free barbed end adopt a flat F-actin conformation, while the CapZ protein undergoes major changes when binding to the barbed end. In contrast, subunits at the free pointed end adopt a twisted monomeric actin conformation, and tropomodulin binding forces the second subunit into an F-actin conformation. These structures reveal the differences between the ends and middle of F-actin and how these differences control various interactions.
Article
Biochemistry & Molecular Biology
Wei Peng, Amanda K. Casey, Jessie Fernandez, Emily M. Carpinone, Kelly A. Servage, Zhe Chen, Yang Li, Diana R. Tomchick, Vincent J. Starai, Kim Orth
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2020)
Article
Multidisciplinary Sciences
Lianying Jiao, Murtada Shubbar, Xin Yang, Qi Zhang, Siming Chen, Qiong Wu, Zhe Chen, Josep Rizo, Xin Liu
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Chemistry, Medicinal
Michael J. Palmer, Xiaoyi Deng, Shawn Watts, Goran Krilov, Aleksey Gerasyuto, Sreekanth Kokkonda, Farah El Mazouni, John White, Karen L. White, Josefine Striepen, Jade Bath, Kyra A. Schindler, Tomas Yeo, David M. Shackleford, Sachel Mok, Ioanna Deni, Aloysus Lawong, Ann Huang, Gong Chen, Wen Wang, Jaya Jayaseelan, Kasiram Katneni, Rahul Patil, Jessica Saunders, Shatrughan P. Shahi, Rajesh Chittimalla, Inigo Angulo-Barturen, Maria Belen Jimenez-Diaz, Sergio Wittlin, Patrick K. Tumwebaze, Philip J. Rosenthal, Roland A. Cooper, Anna Caroline Campos Aguiar, Rafael V. C. Guido, Dhelio B. Pereira, Nimisha Mittal, Elizabeth A. Winzeler, Diana R. Tomchick, Benoit Laleu, Jeremy N. Burrows, Pradipsinh K. Rathod, David A. Fidock, Susan A. Charman, Margaret A. Phillips
Summary: DHODH has been clinically validated as a target for new antimalarials, and a structure-based computationally driven lead optimization program of DHODH inhibitors has led to the discovery of two promising candidates for potential advancement to preclinical development. These compounds exhibit improved physicochemical properties, potent antimalarial activity in vitro, and good efficacy in Plasmodium falciparum SCID mouse models, showing selectivity for Plasmodium DHODHs versus mammalian enzymes.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Ting-Sung Hsieh, Victor A. Lopez, Miles H. Black, Adam Osinski, Krzysztof Pawlowski, Diana R. Tomchick, Jen Liou, Vincent S. Tagliabracci
Summary: During infection, bacterial pathogens can manipulate host cellular membranes by utilizing a self-organizing system involving bacterial kinases and phosphatases, such as the Legionella effector MavQ. This mechanism allows bacteria to hijack host cellular structures for survival by driving rapid turnover of phosphoinositides and inducing vesicle and tubule budding.
Article
Biochemistry & Molecular Biology
Arne Strand, San-Tai Shen, Diana R. Tomchick, Junmei Wang, Chyung-Ru Wang, Johann Deisenhofer
Summary: The presentation of antigenic peptides to T-cell receptors is crucial for the adaptive immune response. Through crystal structure determination and molecular dynamics simulations, researchers found that conformational differences within one microsecond during molecular dynamics simulations of peptide complexes with H2-M3 could be crucial to T-cell discrimination. Specifically, peptide ligands with alanine or threonine at position 6 partially exiting the binding groove could play a key role in the immune response initiation by T cells.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Multidisciplinary Sciences
Konstantinos Nakos, Md Noor A. Alam, Megan R. Radler, Ilona A. Kesisova, Changsong Yang, Joshua Okletey, Meagan R. Tomasso, Shae B. Padrick, Tatyana M. Svitkina, Elias T. Spiliotis
Summary: Cellular morphogenesis and processes such as cell division and migration require the coordination of the microtubule and actin cytoskeletons. This study shows that septins mediate microtubule-actin crosstalk by coupling actin polymerization to microtubule lattices.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Thomas A. Russo, Timothy C. Umland, Xiaoyi Deng, Farah El Mazouni, Sreekanth Kokkonda, Ruth Olson, Ulrike Carlino-MacDonald, Janet Beanan, Cassandra L. Alvarado, Diana R. Tomchick, Alan Hutson, Hong Chen, Bruce Posner, Pradipsinh K. Rathod, Susan A. Charman, Margaret A. Phillips
Summary: New antimicrobials are necessary for treating extensively drug-resistant Acinetobacter baumannii. The results of genetic and chemical studies suggest that the de novo pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase (DHODH) is essential for the survival of this bacterium. By repurposing a library of analogs developed for malaria DHODH program, researchers have identified 21 compounds with potent activity against Acinetobacter baumannii DHODH. One of these compounds, DSM186, has shown promise with minimal inhibitory concentrations against various strains of A. baumannii. These findings highlight the potential of DHODH as a target for the development of new antimicrobials for the treatment of high-risk bacterial infections.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Angela J. Zou, Lisa Kinch, Suneeta Chimalapati, Nalleli Garcia, Diana R. Tomchick, Kim Orth
Summary: This study reveals the mechanism by which pathogenic Vibrio parahaemolyticus senses and responds to bile acids. It was found that the bile acid taurodeoxycholate (TDC) activates the master regulator VtrB, leading to the induction of pathogenesis. Other bile acids, such as chenodeoxycholate (CDC), do not have this activation capability. The study also shows that CDC and TDC compete for binding to the VtrA-VtrC complex, providing insights into the selective pathogenic signaling of V.parahaemolyticus.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Kimberly C. Grasty, Claudia Guzik, Elizabeth J. D'Lauro, Shae B. Padrick, Joris Beld, Patrick J. Loll
Summary: The VanRS two-component system controls the resistance of vancomycin-resistant enterococci. The sensor VanS autophosphorylates and transfers the phosphate group to the response regulator VanR, activating it as a transcription factor for resistance gene expression. Crystal structures of the catalytic and ATP-binding domains of VanS proteins reveal the Bergerat fold seen in other histidine kinases. Interestingly, the domains display low affinities for ATP, suggesting a potential regulatory mechanism for resistance phenotype expression.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Review
Cell Biology
Meagan R. Tomasso, Shae B. Padrick
Summary: The BORG/Cdc42 effector proteins family, consisting of five Rho GTPase binding proteins, has garnered significant interest due to its functions and mechanism of actions. Recent research findings have provided valuable insights into the family as a whole, reshaping our understanding of cellular organization. These studies have linked BORGs to fundamental physiology as well as human diseases, particularly cancers, suggesting that their cancer-promoting properties are related to their regulation of the cytoskeleton. This correlation aligns with existing evidence indicating that BORG family members regulate both the septin and actin cytoskeleton networks. Although the exact mechanism through which BORGs modify the cytoskeleton remains unclear, several data-supported and speculative possibilities have been proposed. Furthermore, the influence of the Rho GTPase Cdc42 on BORG function in cells appears to be cell type- and cell state-dependent, adding complexity to the overall picture. Collectively, these findings emphasize the significance of the BORG family and highlight broader themes in their function and regulation.
Article
Biology
Yun-Zu Pan, Qiren Liang, Diana R. Tomchick, Jef K. De Brabander, Josep Rizo
Summary: Stimulation of autophagy through targeting Bcl-2 binding could be a potential therapy for various diseases. This study describes the NMR structure of Bcl-2 bound to a compound that inhibits Beclin 1/Bcl-2 binding more effectively than Bax/Bcl-2 binding. The structure suggests the possibility of designing compounds that disrupt Beclin 1/Bcl-2 binding and stimulate autophagy without inducing apoptosis.
COMMUNICATIONS BIOLOGY
(2023)
Meeting Abstract
Cardiac & Cardiovascular Systems
Ngoc U. Nguyen, Mahmoud S. Ahmed, Yuji Nakada, Ching-Cheng Hsu, Ayman Farag, Ping Wang, Ivan Menendez-Montes, Suwannee Thet, Nicholas T. Lam, Diana R. Tomchick, Gregory Walcott, Nick V. Grishin, Jianyi J. Zhang, Hesham A. Sadek
CIRCULATION RESEARCH
(2022)
Meeting Abstract
Chemistry, Multidisciplinary
D. R. Tomchick, M. H. Black, A. Osinski, K. Pawlowski, M. Gradowski, Z. Chen, Y. Li, K. A. Servage, V. S. Tagliabracci
ACTA CRYSTALLOGRAPHICA A-FOUNDATION AND ADVANCES
(2021)
Meeting Abstract
Chemistry, Multidisciplinary
Diana Tomchick
ACTA CRYSTALLOGRAPHICA A-FOUNDATION AND ADVANCES
(2021)
Article
Biochemistry & Molecular Biology
Bin Li, Xiaoyi Deng, Sok Ho Kim, Leann Buhrow, Diana R. Tomchick, Margaret A. Phillips, Anthony J. Michael
Summary: The siderophore rhizoferrin is synthesized by fungi and bacteria to scavenge iron. Some bacteria can produce rhizoferrin using a single enzyme, while others use alternative pathways for its biosynthesis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)