Article
Multidisciplinary Sciences
Mengjie Sun, Mingkang Jia, He Ren, Biying Yang, Wangfei Chi, Guangwei Xin, Qing Jiang, Chuanmao Zhang
Summary: In this study, it was shown that NuMA undergoes liquid-liquid phase separation during mitotic entry, condensing on spindle poles and enriching critical components to promote spindle assembly.
NATURE COMMUNICATIONS
(2021)
Article
Biology
John P. Gillies, Janice M. Reimer, Eva P. Karasmanis, Indrajit Lahiri, Zaw Min Htet, Andres E. Leschziner, Samara L. Reck-Peterson
Summary: We report the high-resolution structure of the yeast dynein-Lis1 complex, which reveals the major contacts between dynein and Lis1 and between Lis1's ss-propellers. Structure-guided mutations in Lis1 and dynein show that these contacts are required for Lis1's ability to form fully active human dynein complexes and to regulate yeast dynein's mechanochemistry and in vivo function.
Editorial Material
Biochemistry & Molecular Biology
Sharon R. Garrott, Morgan E. DeSantis
Summary: In this study, Chaaban and Carter employ cryo-electron microscopy and innovative data processing techniques to reveal the high-resolution structure of the dynein-dynactin-BICDR1 complex assembled on microtubules. The structure uncovers novel stoichiometry and offers new insights into the function and mechanism of dynein.
TRENDS IN BIOCHEMICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Vanesa Madan, Lucas Albacete-Albacete, Li Jin, Pietro Scaturro, Joseph L. Watson, Nadine Muschalik, Farida Begum, Jerome Boulanger, Karl Bauer, Michael A. Kiebler, Emmanuel Derivery, Simon L. Bullock
Summary: HEATR5B is a novel player in dynein-dynactin function, directly binding to the dynein tail and dynactin, and stimulating the motility of AP1-associated endosomal membranes. HEATR5B also promotes association of AP1 with endosomal membranes independently of dynein.
Article
Biophysics
Xiaodong Cheng, Kuangcai Chen, Bin Dong, Seth L. Filbrun, Gufeng Wang, Ning Fang
Summary: A bifocal parallax single-particle tracking method has been developed to resolve coordinated biomolecular interactions in complex living cell environments in real time. This method allows for full-range azimuth angle and 3D displacement of cargo in the cell cytoskeleton, revealing new interactions and providing insights into the dynamics of cargo-motor-track interactions in different types of microtubule intersections.
BIOPHYSICAL JOURNAL
(2021)
Article
Neurosciences
Amrita Mandal, Hiu-Tung C. Wong, Katherine Pinter, Natalie Mosqueda, Alisha Beirl, Richa Madan Lomash, Sehoon Won, Katie S. Kindt, Catherine M. Drerup
Summary: Research shows that retrograde mitochondrial transport plays a crucial role in maintaining the homeostatic distribution of mitochondria in neurons, and disrupting this process can lead to accumulation of aged organelles in axon terminals and loss of mitochondria in the cell body.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Paulomi Sanghavi, Pankaj Kumar, Ankit Roy, M. S. Madhusudhan, Roop Mallik
Summary: Disrupting the interactions between dynactin and dynein or microtubules impacts dynein's behavior on microtubules and its ability to generate force. The dynactin-microtubule link is shown to be crucial for dynein's persistence against load, shedding light on dynein dysfunction.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Xiangyu Fan, Richard J. McKenney
Summary: This study reveals the crucial role of a specialized kinesin tail domain in directing motor transport along specific microtubule tracks. The tail domain affects the initial motor-microtubule interaction and the processive motility, and its effect is enhanced when the motor domain is in the ADP state.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Mangal Deep Burman, Sagar Bag, Souvik Ghosal, Sudip Karmakar, Goutam Pramanik, Raj Kumar Chinnadurai, Sudipta Bhowmik
Summary: In this study, the interaction between hemoglobin and the plant alkaloids harmine and harmaline was investigated. The results showed that harmine had a stronger interaction with hemoglobin compared to harmaline. The motional restriction of harmine in the presence of hemoglobin was also higher than that of harmaline. Additionally, harmine exhibited a stronger affinity for hemoglobin. The study also revealed that both harmine and harmaline had a slight effect on the stability of hemoglobin. These findings provide important insights into the interaction properties of harmine and harmaline, which may be valuable in drug discovery processes.
Article
Biology
Ines Hernandez-Perez, Javier Rubio, Adrian Baumann, Henrique Girao, Miriam Ferrando, Elena Rebollo, Anna M. Aragay, Maria Isabel Geli
Summary: This study found that Kazrin plays an important role in vertebrate development, including cell adhesion, migration, and endocytic trafficking. The isoform Kazrin C was identified as a potent inhibitor of clathrin-mediated endocytosis when overexpressed. By generating Kazrin knockout mouse embryonic fibroblasts, the researchers discovered that Kazrin depletion delays the transport of internalized material and impairs the retrograde motility of early endosomes. Further analysis revealed that the C-terminal domain of Kazrin C interacts with early endosome components and that the N-terminus shares homology with dynein/dynactin adaptors. Overall, these findings suggest that Kazrin facilitates endocytic recycling by promoting dynein/dynactin-dependent transport of early endosomes or their derivatives.
Article
Multidisciplinary Sciences
Luke S. Ferro, Qianglin Fang, Lisa Eshun-Wilson, Jonathan Fernandes, Amanda Jack, Daniel P. Farrell, Mert Golcuk, Teun Huijben, Katelyn Costa, Mert Gur, Frank DiMaio, Eva Nogales, Ahmet Yildiz
Summary: Research has found that MAP7 is a required cofactor for kinesin-1-driven transport of intracellular cargoes. MAP7 binds to microtubules (MTs) and facilitates kinesin-1 motility, but it also inhibits kinesin-1 motility by partially overlapping with its binding site. However, by tethering kinesin-1 to the MT, MAP7 prevents dissociation of the motor and facilitates its binding to other available sites. This biphasic regulation of kinesin-1 by MAP7 becomes dominant when MTs are saturated with MAP7.
Article
Multidisciplinary Sciences
Kyoko Okada, Bharat R. Iyer, Lindsay G. Lammers, Pedro A. Gutierrez, Wenzhe Li, Steven M. Markus, Richard J. Mckenney
Summary: This study reveals previously unknown steps in the activation pathway of cytoplasmic dynein-mediated cargo transport and provides insight into the integrated activities of LIS1/Ndel1 and dynactin/cargo-adapters. The findings contribute to the understanding of the roles of the human disease genes Ndel1 and LIS1 in the assembly and activation of dynein transport complexes.
NATURE COMMUNICATIONS
(2023)
Review
Cell Biology
Sydney E. Cason, Erika L. F. Holzbaur
Summary: The active transport of organelles and other cargos along the axon is essential for maintaining neuronal health and function. However, the complex regulatory mechanisms involved in this process are still not fully understood. This review discusses the current understanding of motor regulation in axonal transport and explores how regulatory proteins affect the activity of dynein or kinesin motors. The specific mechanisms that regulate motor activity during organelle trafficking in the axon are also highlighted.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2022)
Article
Cell Biology
Sandra Tavares, Nalan Liv, Milena Pasolli, Mark Opdam, Max A. K. Ratze, Manuel Saornil, Lilian M. Sluimer, Rutger C. C. Hengeveld, Robert van Es, Erik van Werkhoven, Harmjan Vos, Holger Rehmann, Boudewijn M. T. Burgering, Hendrika M. Oosterkamp, Susanne M. A. Lens, Judith Klumperman, Sabine C. Linn, Patrick W. B. Derksen
Summary: Elevated expression of non-receptor tyrosine kinase FER is associated with poor prognosis in breast cancer patients, particularly in high-grade and basal/triple-negative cases. However, high FER levels are correlated with improved outcomes after adjuvant taxane-based chemotherapy in high-risk, HER2-negative patients. Mechanistic studies reveal that FER regulates endosomal recycling and its inhibition leads to reduced breast cancer cell invasion. Furthermore, DCTN2 is identified as a substrate of FER, and its phosphorylation at tyrosine 6 is essential for tubular recycling domains formation and TNBC cell invasion.
Article
Biophysics
Jesse Howe, Austin Weeks, Patrick Reardon, Elisar Barbar
Summary: A new study reveals that 53BP1 protein has three binding sites for LC8, which is contrary to previous findings. The third site, located near the oligomerization domain of 53BP1, challenges our current understanding of the role of LC8 in the function of 53BP1.
BIOPHYSICAL JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Nikolaus M. Loening, Elisar Barbar
Summary: Swallow, a 62 kDa multidomain protein, plays a critical role in the proper localization of several mRNAs involved in Drosophila oocyte development. Dimerization of Swallow is dependent on a 71-residue self-association domain and is stabilized by its binding interaction with dynein light chain (LC8). The structure of the self-association domain has been characterized using solution-state nuclear magnetic resonance spectroscopy, revealing a parallel coiled-coil structure and providing insight into the regulation of dimerization stability.
Article
Zoology
Katharine A. White, Kira D. McEntire, Nicole R. Buan, Lecia Robinson, Elisar Barbar
Summary: Advances in quantitative biology data collection and analysis have transformed our understanding of complex biological systems across different scales; however, the disconnect between mathematical modeling and experimental biology limits our full potential in utilizing mathematical models for better understanding of biological systems.
INTEGRATIVE AND COMPARATIVE BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jessica L. Morgan, Andrew Yeager, Aidan B. Estelle, Jorg Gsponer, Elisar Barbar
Summary: The N-terminal domain of dynein intermediate chain (N-IC) is a prototypical intrinsically disordered protein (IDP) that serves as a molecular scaffold for binding partners. Tertiary interactions in N-IC underlie differences in interactions with dynein partners p150(Glued) and NudE, showing that tertiary and secondary structures are coupled in IDPs. Interactions are attenuated when N-IC is bound to NudE, shifting the conformational ensemble to a more extended state with less structure.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Editorial Material
Biochemistry & Molecular Biology
Elisar Barbar, Aidan Estelle
Summary: The study presents NMR structures of BET: MLV IN complexes, shedding light on the role of the disordered tail domain of MLV IN in viral integration. It expands the understanding of molecular recognition polymorphism in BET complexes and provides insights for cancer and antiviral therapeutics.
Article
Biochemistry & Molecular Biology
Aidan B. Estelle, Patrick N. Reardon, Seth H. Pinckney, Leslie B. Poole, Elisar Barbar, P. Andrew Karplus
Summary: Peroxiredoxins are enzymes that play important roles in detoxification and redox signaling. Through nuclear magnetic resonance spectroscopy, it has been discovered that Xanthomonas campestris peroxiredoxin Q undergoes local unfolding and dynamics at its active site, which is likely relevant to its catalytic activity.
Article
Biochemistry & Molecular Biology
Joaquin Rodriguez Galvan, Brianna Donner, Cat Hoang Veseley, Patrick Reardon, Heather M. Forsythe, Jesse Howe, Gretchen Fujimura, Elisar Barbar
Summary: The study reveals that HPIV3 phosphoprotein exists as a stable α-helical tetramer in solution, and interacts with host protein LC8 to regulate its solubility. Comparative analysis shows multiple binding motifs of LC8 with various virus phosphoproteins, highlighting its importance in regulating viral function.
Article
Biochemistry & Molecular Biology
Barmak Mostofian, Russell McFarland, Aidan Estelle, Jesse Howe, Elisar Barbar, Steve L. Reichow, Daniel M. Zuckerman
Summary: This study developed an automated single-particle electron microscopy pipeline for analyzing 'beads-on-a-string' assemblies. The approach quantifies conformational geometries and compositional heterogeneity on a single-particle basis and corrects spurious observations. Applied to nuclear pore IDP and transcription factor, the analysis revealed compositional and conformational diversity in both systems.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Cat Hoang Vesely, Patrick N. Reardon, Zhen Yu, Elisar Barbar, Ryan A. Mehl, Richard B. Cooley
Summary: Phosphoserine (pSer) sites are primarily located within disordered protein regions. Producing labeled proteins with site-specific pSer for NMR studies is important for understanding the molecular mechanisms of protein regulation. However, methodologies for adapting pSer genetic code expansion to minimal or isotope-enriched media have not been described.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biophysics
Jesse Howe, Austin Weeks, Patrick Reardon, Elisar Barbar
Summary: A new study reveals that 53BP1 protein has three binding sites for LC8, which is contrary to previous findings. The third site, located near the oligomerization domain of 53BP1, challenges our current understanding of the role of LC8 in the function of 53BP1.
BIOPHYSICAL JOURNAL
(2022)
Article
Biology
Kayla A. Jara, Nikolaus M. Loening, Patrick N. Reardon, Zhen Yu, Prajna Woonnimani, Coban Brooks, Cat H. Vesely, Elisar J. Barbar
Summary: Cytoplasmic dynein is crucial for intracellular transport, with its intermediate chain (IC) regulating interactions with p150(Glued) and NudE. The multivalent binding of light chains modulates autoinhibition, highlighting their importance in IC assembly and organization.
Meeting Abstract
Biophysics
Jesse J. Howe, Patrick N. Reardon, Elisar J. Barbar
BIOPHYSICAL JOURNAL
(2022)
Meeting Abstract
Biophysics
Aidan Estelle, August George, Elisar J. Barbar, Daniel M. Zuckerman
BIOPHYSICAL JOURNAL
(2022)
Meeting Abstract
Biophysics
Aidan Estelle, Patrick N. Reardon, Andrew Karplus, Elisar J. Barbar
BIOPHYSICAL JOURNAL
(2021)
Meeting Abstract
Biophysics
Kayla A. Jara, Nikolaus M. Loening, Elisar J. Barbar
BIOPHYSICAL JOURNAL
(2021)
Meeting Abstract
Biophysics
Barmak Mostofian, Russell McFarland, Aidan Estelle, Jesse J. Howe, Elisar J. Barbar, Steve L. Reichow, Daniel M. Zuckerman
BIOPHYSICAL JOURNAL
(2021)