Article
Biophysics
George Khelashvili, Ambrose Plante, Milka Doktorova, Harel Weinstein
Summary: Studies have shown that the fusion peptide (FP) of coronaviruses requires binding of Ca2+ ions to enhance penetration, but the mechanisms of membrane insertion and destabilization remain unclear.
BIOPHYSICAL JOURNAL
(2021)
Article
Multidisciplinary Sciences
Li Wang, Kangjing Chen, Zhucheng Chen
Summary: ALC1, an oncogenic chromatin remodeler, plays a crucial role in DNA repair by relaxing chromatin. The study reveals the crystal structure of ALC1 and how it is activated by binding to nucleosomes.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Yang Zhou, Hui Yan, Qiang Zhou, Penggao Wang, Fang Yang, Ziqiao Yuan, Qianming Du, Bo Zhai
Summary: The study found that CCNB1IP1 is upregulated in MYCN-amplified neuroblastoma and is associated with poor prognosis. CCNB1IP1 cooperates with MYCN to promote proliferation and tumorigenicity in neuroblastoma. This study also revealed a previously uncharacterized mechanism of CCNB1IP1-mediated MYCN protein stability, providing new prospects for precise treatment of MYCN-amplified neuroblastoma.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Desiree M. Baron, Adam R. Fenton, Sara Saez-Atienzar, Anthony Giampetruzzi, Aparna Sreeram, Shankaracharya, Pamela J. Keagle, Victoria R. Doocy, Nathan J. Smith, Eric W. Danielson, Megan Andresano, Mary C. McCormack, Jaqueline Garcia, Valerie Bercier, Ludo Van den Bosch, Jonathan R. Brent, Claudia Fallini, Bryan J. Traynor, Erika L. F. Holzbaur, John E. Landers
Summary: Understanding the pathogenic mechanisms of disease mutations is crucial for advancing treatments. This study found that ALS-associated mutations in the gene encoding microtubule motor KIF5A result in the production of a protein with an abnormal C-terminal sequence, leading to motor activity dysregulation and decreased neuronal survival. These findings shed light on the disruptive effects of pathogenic mutations on intracellular trafficking and neuronal homeostasis.
Article
Biology
Keijun Kakihara, Kengo Asamizu, Kei Moritsugu, Masahide Kubo, Tetsuya Kitaguchi, Akinori Endo, Akinori Kidera, Mitsunori Ikeguchi, Akira Kato, Masayuki Komada, Toshiaki Fukushima
Summary: This study identified amino acids 645-684 of USP8 as an autoinhibitory region and suggested that the release of USP8 autoinhibition may underlie Cushing's disease. The findings also indicate that 14-3-3 inhibits USP8 activity partly by enhancing the interaction between the WW-like and USP domains.
COMMUNICATIONS BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Wenjuan Wang, Jinqi Ren, Weiye Song, Yong Zhang, Wei Feng
Summary: This study reveals the autoinhibition mechanism of kinesin-3 KLP6, in which the internal coiled-coil segments and domains cooperate to lock down the neck and motor domains, ensuring proper spatiotemporal control of intracellular transport.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Tianyi Yang, Li Han, Shuanghong Huo
Summary: This study investigates the conformational changes and allosteric signal transmission pathways of human c-Cbl protein during substrate binding using molecular dynamics simulations. The results show that Phe378 and the C-terminal region play a crucial role in stabilizing the partially open state, while bottlenecks are found at the junctions between the SH2 domain and the linker helix region and between the SH2 domain and the 4H bundle. The findings provide valuable insights for drug discovery, particularly in targeted protein degradation strategies.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Multidisciplinary Sciences
Hammam Antar, Young-Min Soh, Stefano Zamuner, Florian P. Bock, Anna Anchimiuk, Paolo De los Rios, Stephan Gruber
Summary: Three-component ParABS systems play important roles in plasmid partitioning and chromosome segregation in bacteria, with ParB acting as a crucial adaptor protein. CTP hydrolysis is essential for efficient chromosome segregation by ParABS, contributing to partition complex assembly through two mechanisms.
Article
Chemistry, Multidisciplinary
Paul Stahl, Sebastian Kollenda, Jonas Sager, Laura Schmidt, Martin A. Schroer, Roland H. Stauber, Matthias Epple, Shirley K. Knauer
Summary: A nanobody (SuN) targeting the disease-relevant protein Survivin is used to track its concentration inside cells but fails to inhibit its biological functions. The coupling of multiple SuN to ultra-small gold nanoparticles (SuN-N) enables intracellular uptake and interference with mitotic progression. This demonstrates the universal applicability of coupling nanobodies to nanosized scaffolds to improve their function and therapeutic applicability.
Article
Biochemistry & Molecular Biology
Laszlo Imre, Erfaneh Firouzi Niaki, Rosevalentine Bosire, Peter Nanasi, Peter Nagy, Zsolt Bacso, Nubar Hamidova, Yves Pommier, Albert Jordan, Gabor Szabo
Summary: This study explores the roles and interactions of polyamines (PAs) in the nucleus, specifically their effect on nucleosome stability. The results demonstrate that PAs, such as spermine, spermidine, and putrescine, have a strong destabilizing effect on nucleosomes in the millimolar concentration range. This effect is dependent on pH and salt concentration, and remains significant even at neutral pH. It was also found that PA treatment does not affect the integrity of genomic DNA. Furthermore, the study shows that PAs bind to DNA, as evidenced by the displacement of ethidium bromide.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2022)
Article
Physics, Fluids & Plasmas
P. Hayoun, A. Letailleur, J. Teisseire, F. Lequeux, E. Verneuil, E. Barthel
Summary: For partially wetting fluids, the thickness and dewetting velocity of gravity-driven films are determined by triple line dynamics. However, when flushing aqueous liquids through polymer tubes, the dewetting velocity and thickness can be selected based on the control parameter of pressure, i.e., the macroscopic curvature of the meniscus. This study directly demonstrates the significant role played by macroscopic geometry in the stability of a dynamic meniscus, as predicted by Eggers.
PHYSICAL REVIEW FLUIDS
(2022)
Article
Chemistry, Multidisciplinary
Zheyi An, Hiroko Yokota, Kyomaru Kurihara, Nozomu Hasegawa, Pavel Marton, Anthony Michael Glazer, Yoshiaki Uesu, Wei Ren, Zuo-Guang Ye, Marek Pasciak, Nan Zhang
Summary: A tunable polar domain boundary is discovered in an antiferroelectric single crystal, where the density, volume, and polarity of the boundaries can be controlled under a small stress or electric field.
ADVANCED MATERIALS
(2023)
Article
Multidisciplinary Sciences
Alena Randakova, Dominik Nelic, Jan Jakubik
Summary: This study investigates potential problems in the parsimonious operational model of agonism (OMA) and compares the fitting performance of OMA based on the Hill equation and the Black & Leff equation in cases where functional-response curves differ in the slope factor. The conclusion is that Hill equation-based OMA should be preferred in such cases.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Yanli Dong, Hang Li, Alina Ilie, Yiwei Gao, Annie Boucher, Xuejun Cai Zhang, John Orlowski, Yan Zhao
Summary: Sodium-proton exchanger 3 (NHE3/SLC9A3) plays an important role in regulating salt and fluid absorption as well as pH homeostasis. Calcineurin B homologous protein 1 (CHP1) acts as an auxiliary regulatory factor for NHE3, promoting its maturation and plasmalemmal expression. Cryo-electron microscopy structure analysis revealed that a cytosolic helix-loop-helix motif in NHE3 inhibits substrate transport, and the binding of phosphatidylinositol molecules stabilizes the complex and enhances its transport activity.
Article
Biology
Serah W. Kimani, Sumera Perveen, Magdalena Szewezyk, Hong Zeng, Aiping Dong, Fengling Li, Pegah Ghiabi, Yanjun Li, Irene Chau, Cheryl H. Arrowsmith, Dalia Barsyte-Lovejoy, Vijayaratnam Santhakumar, Masoud Vedadi, Levon Halabelian
Summary: Cbl-b, a RING-type E3 ubiquitin ligase, negatively regulates immune cell activity and is considered an attractive target for cancer immunotherapy. A novel Cbl-b inhibitor, C7683, binds strongly to Cbl-b and inhibits its activity by locking the protein in an inactive conformation. This study provides structural insights into the inhibition mechanism of Cbl-b.
COMMUNICATIONS BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Hai T. Dao, Hengyuan Liu, Nazar Mashtalir, Cigall Kadoch, Tom W. Muir
Summary: This study reports a strategy for controlling the orientation of asymmetric nucleosomes and hexasomes, providing an efficient method for studying gene regulation. By using truncated DNA templates and DNA ligation, the researchers successfully prepared desymmetrized mononucleosomes and oligonucleosomes with varied DNA sequences and histone compositions. Using this technology, they investigated the impact of asymmetry on chromatin remodeling and found that cancer-associated histone mutations can cause aberrant chromatin structure.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Bradley J. Lukasak, Robert E. Thompson, Michelle M. Mitchener, Vanessa J. Feng, John D. Bagert, Tom W. Muir
Summary: In this study, the SpyCatcher/SpyTag system was used to assemble desymmetrized nucleoprotein complexes. This method allows for the generation of nucleosomes with asymmetric modifications and facilitates the investigation of the effects of nucleosome asymmetry on chromatin remodeling processes and histone enzyme activity.
ACS CENTRAL SCIENCE
(2022)
Correction
Biochemistry & Molecular Biology
Ming-Hao Li, Lakshan Manathunga, Erwin London, Daniel P. Raleigh
Article
Chemistry, Multidisciplinary
Alyssa Dubrow, Bryan Zuniga, Elias Topo, Jae-Hyun Cho
Summary: The study identifies a new NSB blocker that effectively suppresses nonspecific binding between analytes and biosensors, making it significant for quantitative analysis of weak PPIs.
Article
Endocrinology & Metabolism
Joseph J. Castillo, Alfred C. Aplin, Daryl J. Hackney, Meghan F. Hogan, Nathalie Esser, Andrew T. Templin, Rehana Akter, Steven E. Kahn, Daniel P. Raleigh, Sakeneh Zraika, Rebecca L. Hull
Summary: The study found that aggregation of IAPP is toxic to islet endothelial cells and induces inflammatory responses, resulting in decreased capillary density, increased capillary diameter, and an increased number of pericytes.
Article
Biochemistry & Molecular Biology
Lakshan Manathunga, Alexander Zhyvoloup, Aria Baghai, Daniel P. Raleigh
Summary: Islet amyloid polypeptide (IAPP) is a 37-residue polypeptide hormone secreted by pancreatic β-cells. It plays a role in glycemic regulation, but in the pre-type-2 diabetic state, it forms amyloid aggregates that contribute to β-cell dysfunction and disease progression. This study investigates the role of aromatic residues in modulating the time course of amyloid formation and cytotoxicity. The results reveal that F23 plays a dominant role and has both accelerating and slowing effects on amyloid formation, as well as influences toxicity.
Article
Biochemistry & Molecular Biology
Matthew E. T. Miller, Ming-Hao Li, Aria Baghai, Vincent H. Peetz, Alexander Zhyvoloup, Daniel P. Raleigh
Summary: Human islet amyloid polypeptide (hIAPP) plays a significant role in the development of diabetes and beta-cell dysfunction. Sheep and goat IAPP have low amyloid formation and toxicity compared to hIAPP. Studying IAPP from different species can provide insights for designing soluble analogues of the human peptide.
Article
Chemistry, Multidisciplinary
Giridhar Sekar, Adam J. Stevens, Anahita Z. Mostafavi, Pulikallu Sashi, Tom W. Muir, David Cowburn
Summary: Split intein-mediated protein trans-splicing (PTS) is a widely used method in chemical biology and biotechnology for traceless and specific protein ligation. The efficiency of PTS can be limited by external residues flanking the intein. In this study, a recently developed atypically split intein (Cat) was further modified to enhance its PTS activity in the presence of unfavorable N-extein residues. The mechanism behind the enhanced activity was explored using nuclear magnetic resonance spectroscopy and molecular dynamics simulations, highlighting the contribution of a conserved histidine residue. This enhanced extein tolerance of Cat* expands the applicability of atypically split inteins and reveals common principles of extein dependence.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Review
Biochemistry & Molecular Biology
Michelle M. Mitchener, Tom W. Muir
Summary: Research over the past decade has revealed a new layer of epigenetic dysregulation, uncovering the association between somatic missense mutations in histones and human pathologies, especially cancer. While some of these mutations are believed to be key drivers of cancer, the effects of the majority of them on disease onset and progression are still unclear. Studies have shown that even at low dosage, histone mutants can corrupt chromatin states, providing insights into the intricate mechanisms of epigenetic control.
Article
Multidisciplinary Sciences
Iktae Kim, Alyssa Dubrow, Bryan Zuniga, Baoyu Zhao, Noah Sherer, Abhishek Bastiray, Pingwei Li, Jae-Hyun Cho
Summary: Investigated the influence of strain-specific mutations on the evolution of influenza viruses and found that these mutations play a crucial role in shaping the protein energy landscape and altering the conformational dynamics of tightly packed residues.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Analytical
Konstantinos Thalassinos, Charles Eldrid, Tristan Cragnolini, Aisha Ben-Younis, Junjie Zou, Daniel P. . Raleigh
Summary: Native mass spectrometry combined with ion mobility and collisional activation is an important method for studying protein unfolding. By using unbiased molecular dynamics simulations, the in vacuo unfolding behavior of a well-studied protein, N-terminal domain of ribosomal L9, was found to replicate the behavior observed in solution. However, the theoretical collision cross section of the simulations was slightly lower than that of the experimental data, possibly due to reduced sampling.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Lakshan Manathunga, Rehana Akter, Alexander Zhyvoloup, Carlos Simmerling, Daniel P. P. Raleigh
Summary: Amyloids are protein deposits implicated in various diseases. Disrupting the tight packing in amyloid fibrils affects their formation kinetics. Substitutions with larger amino acids disrupt packing and destabilize fibril structures, while specific substitutions can enhance or slow down amyloid formation.
Article
Chemistry, Physical
Jie Shi, Jae-Hyun Cho, Wonmuk Hwang
Summary: We develop a computational method to evaluate the solvation free energy based on the density map of the first hydration shell constructed from molecular dynamics simulation. The binding of two ligands to their target protein is examined, and it is found that the viral ligand incurs a lower desolvation penalty and exhibits stronger binding affinity than the human ligand. The difference in desolvation penalty is attributed to the spatially fragmented and nonuniform water density profiles of the first hydration shell.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Biochemical Research Methods
Henry M. Sanders, Farzaneh Chalyavi, Caitlyn R. Fields, Marius M. Kostelic, Ming-Hao Li, Daniel P. Raleigh, Martin T. Zanni, Michael T. Marty
Summary: The aggregation of islet amyloid polypeptide (IAPP) is associated with beta-cell dysfunction in type 2 diabetes (T2D) in humans. The interaction of IAPP oligomers with lipid membranes can disrupt the bilayer integrity and/or homeostasis of the cell. Amino acid sequence variations of IAPPs between species can greatly decrease their propensity for aggregation.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2023)
Article
Cell Biology
David Anaguano, Watcharatip Dedkhad, Carrie F. Brooks, David W. Cobb, Vasant Muralidharan
Summary: The malaria-causing parasite, Plasmodium falciparum, remodels its host red blood cell by exporting membrane proteins. The process of extracting and exporting these membrane proteins from the parasite plasma membrane remains unknown. This study identified candidate proteins that may be involved in this process and showed that they are essential for parasite growth.
JOURNAL OF CELL SCIENCE
(2023)