Article
Biochemistry & Molecular Biology
Samantha Schrecke, Yun Zhu, Jacob W. McCabe, Mariah Bartz, Charles Packianathan, Minglei Zhao, Ming Zhou, David Russell, Arthur Laganowsky
Summary: The study shows that the two isoforms of K(2P)4.1 have distinct preferences for binding to lipids, including acyl chain length, position, and fatty acid linkage. Phosphatidic acid has the best activation effect on the channel.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Biophysics
Lukas Braun, Ingmar Schoen, Viola Vogel
Summary: Our study utilized a multiscale molecular dynamics simulation approach to investigate the interaction between the vinculin tail and PIP2-enriched membranes, revealing the incompatibility between membrane binding and intramolecular interaction, and identifying two main PIP2 interaction sites. Additionally, by introducing a valency-disaggregated binding network analysis, we were able to map protein-lipid interactions in unprecedented detail.
BIOPHYSICAL JOURNAL
(2021)
Article
Cell Biology
Yun Chen, Ying-Han Wang, Yi Zheng, Meijing Li, Bing Wang, Qiu-Wen Wang, Chong-Lei Fu, Yao-Nan Liu, Xueming Li, Jun Yao
Summary: Synaptic vesicle docking is a dynamic multi-stage process essential for efficient neurotransmitter release. In mouse hippocampal synapses, SV docking is initiated by Syt1 at approximately 12 nm to the active zone, with PI(4,5)P2 being the membrane partner of Syt1. The SNARE complex contributes only to tight SV docking within 0-2 nm.
Article
Multidisciplinary Sciences
Alex J. Flynn, Svetlana V. Antonyuk, Robert R. Eady, Stephen P. Muench, S. Samar Hasnain
Summary: The cryoEM structure of qNOR from Alcaligenes xylosoxidans provides insights into its crucial role in the denitrification pathway and sheds light on the mechanisms of electron, substrate, and proton transport.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Clare. R. Harwood, David A. Sykes, Bradley L. Hoare, Franziska M. Heydenreich, Romez Uddin, David R. Poyner, Stephen J. Briddon, D. B. Veprintsev
Summary: The study demonstrated the isolation of beta 2-adrenoceptor (beta 2AR) using a polymer, diisobutylene maleic acid (DIBMA), which showed improved functional and thermal stability compared to traditional detergent methods. This unique method offers significant advantages for biophysical studies of beta 2AR.
Article
Chemistry, Physical
Gyehyun Park, Myung Keun Cho, YounJoon Jung
Summary: The study proposes a theoretical model and performs molecular dynamics simulations to quantify the sequence-dependent kink probability of strongly bent DNA. Results show that sequences with TA dinucleotide repeats flanked by GC steps increase kink propensity, and the number of base pairs involved in local opening is coupled with sequence-specific bubble formation free energy.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
Article
Chemistry, Physical
Pei Qiao, Samantha Schrecke, Thomas Walker, Jacob W. McCabe, Jixing Lyu, Yun Zhu, Tianqi Zhang, Smriti Kumar, David Clemmer, David H. Russell, Arthur Laganowsky
Summary: This study used variable-temperature native mass spectrometry to investigate the thermodynamics of lipid binding events to the human G-protein-gated inward rectifier potassium channel, Kir3.2, revealing distinct thermodynamic strategies for different types of phosphatidylinositol and phosphorylated forms. The acyl chain of the lipid and the number of phosphate groups have significant impacts on the binding thermodynamics, with entropy and enthalpy playing key roles in the interactions.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Article
Multidisciplinary Sciences
Nan Wang, Shuo Zhang, Yafei Yuan, Hanwen Xu, Elisabeth Defossa, Hans Matter, Melissa Besenius, Volker Derdau, Matthias Dreyer, Nis Halland, Kaihui Hu He, Stefan Petry, Michael Podeschwa, Norbert Tennagels, Xin Jiang, Nieng Yan
Summary: Human glucose transporters (GLUTs), specifically GLUT1 and GLUT3, are potential targets for anticancer therapy. In this study, an engineered GLUT3 variant was used to identify and understand the inhibitory mechanism of an exofacial GLUT3 inhibitor, SA47. This research provides a foundation for the discovery of exofacial inhibitors of GLUTs for therapeutic development.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Takunari Kiya, Kohei Takeshita, Akira Kawanabe, Yuichiro Fujiwara
Summary: It has been found that phosphoinositides (PIPns), a type of membrane lipid, can modulate the function of ion channel KcsA in cell signaling. By investigating the correlation between PIPns and KcsA, it was observed that the open probability of KcsA significantly increased when the membrane contained only a small percentage of PIPns, and this increase was correlated with an increase in negative charges on PIPns.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Manuel Cordova, Lyndon Emsley
Summary: The determination of the molecular solid structure using NMR crystallography relies on generating a comprehensive set of candidate crystal structures and comparing computed chemical shifts with experimental values. However, exploring the polymorph landscape of molecular solids requires a significant computational power, leading to a bottleneck in candidate crystal generation. This study constructs three-dimensional interaction maps using a crystal structure database with associated chemical shifts to identify structural constraints for accelerating crystal structure prediction protocols, without requiring DFT-level chemical shift computations.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
Ruitao Jin, Sitong He, Katrina A. Black, Oliver B. Clarke, Di Wu, Jani R. Bolla, Paul Johnson, Agalya Periasamy, Ahmad Wardak, Peter Czabotar, Peter M. Colman, Carol Robinson, Derek Laver, Brian J. Smith, Jacqueline M. Gulbis
Summary: This paper reveals the gating mechanism of potassium channels and how ion conduction is controlled by anionic lipids. The study demonstrates that anionic lipids interact with the steric plug within the ion conduction pathway, operating the gate. This research is of great significance for our understanding of the gating mechanism of potassium channels.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
David B. Sauer, Jennifer J. Marden, Joseph C. Sudar, Jinmei Song, Christopher Mulligan, Da-Neng Wang
Summary: In this study, the authors demonstrate that the VcINDY protein couples sodium and substrate binding through a cooperative mechanism by conformational selection. The results provide strong evidence for the sodium-dependent formation of the substrate binding site.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Miranda N. Limbach, Aleksandra Antevska, Damilola S. Oluwatoba, Amber L. H. Gray, Xian B. Carroll, Christina M. Hoffmann, Xiaoping Wang, Markus W. Voehler, Carlos A. Steren, Thanh D. Do
Summary: An atomic view of the main aqueous conformation of cyclosporine A (CycA) has been obtained using X-ray and single-crystal neutron diffraction, revealing multiple conformers and providing insight into the membrane permeability and binding of CycA.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Jeremy Scelle, Hugo Vervoitte, Laurent Bouteiller, Lise-Marie Chamoreau, Matthieu Sollogoub, Guillaume Vives, Bernold Hasenknopf
Summary: The encapsulation of guests in a confined space can lead to unusual conformations and reactivities. This study focuses on the effect of a cyclodextrin (CD) dimer cavity on the conformation of alpha,omega-alkyl-diphosphate axles in pseudorotaxane architectures. Results show that in both solid and solution states, the CD can compress the alkyl chain, resulting in conformational changes.
Article
Chemistry, Multidisciplinary
Robert W. Harkness, Zev A. Ripstein, Justin M. Di Trani, Lewis E. Kay
Summary: DegP is a periplasmic protein involved in the transport of pathogenicity-related virulence factors. It functions as a bi-functional protease and chaperone to maintain protein homeostasis in Gram-negative bacteria under stress conditions. It forms cage-like structures by reorganizing high-order preformed apo oligomers, which can encapsulate clients of various sizes.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Antonio Marzio, Joseph Puccini, Youngho Kwon, Natalia K. Maverakis, Arnaldo Arbini, Patrick Sung, Dafna Bar-Sagi, Michele Pagano
Article
Biochemistry & Molecular Biology
Shipra Das, Dafna Bar-Sagi
Article
Cell Biology
Lidong Wang, Huibin Yang, Andrea Zamperone, Daniel Diolaiti, Phillip L. Palmbos, Ethan Abel, Vinee Purohit, Igor Dolgalev, Andrew D. Rhim, Mats Ljungman, Christina H. Hadju, Christopher J. Halbrook, Dafna Bar-Sagi, Marina Pasca di Magliano, Howard C. Crawford, Diane M. Simeonel
GENES & DEVELOPMENT
(2019)
Article
Oncology
Shipra Das, Beny Shapiro, Emily A. Vucic, Sandra Vogt, Dafna Bar-Sagi
Article
Multidisciplinary Sciences
Craig Ramirez, Andrew D. Hauser, Emily A. Vucic, Dafna Bar-Sagi
Article
Biochemistry & Molecular Biology
Daniel Y. Yoo, Andrew D. Hauser, Stephen T. Joy, Dafna Bar-Sagi, Paramjit S. Arora
ACS CHEMICAL BIOLOGY
(2020)
Article
Oncology
Seth J. Parker, Caroline R. Amendola, Kate E. R. Hollinshead, Qijia Yu, Keisuke Yamamoto, Joel Encarnacion-Rosado, Rebecca E. Rose, Madeleine M. LaRue, Albert S. W. Sohn, Doug E. Biancur, Joao A. Paulo, Steven P. Gygi, Drew R. Jones, Huamin Wang, Mark R. Philips, Dafna Bar-Sagi, Joseph D. Mancias, Alec C. Kimmelman
Article
Chemistry, Multidisciplinary
Daniel Y. Yoo, Stephanie A. Barros, Gordon C. Brown, Christian Rabot, Dafna Bar-Sagi, Paramjit S. Arora
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2020)
Editorial Material
Oncology
Rafael Winograd, Diane M. Simeone, Dafna Bar-Sagi
Summary: Immune checkpoint blockade has shown efficacy in multiple cancers, but further improvements are needed to increase response rates and achieve clinical efficacy in cold tumors. Mechanistic studies of tumor-specific immunosuppressive pathways can uncover biological barriers to immunotherapy and offer new therapeutic insights.
BRITISH JOURNAL OF CANCER
(2021)
Article
Cell Biology
Despina Siolas, Emily Vucic, Emma Kurz, Cristina Hajdu, Dafna Bar-Sagi
Summary: Tumor genotype can influence the immune microenvironment in pancreatic cancer, leading to changes in immune cell populations and affecting treatment outcomes. Depletion of neutrophils in CRISPR Kras(G12D/+);Trp53(R172H/+) tumors can enhance the efficacy of CD40 immunotherapy and chemotherapy.
Article
Biochemistry & Molecular Biology
Antonio Marzio, Emma Kurz, Jennifer M. Sahni, Giuseppe Di Feo, Joseph Puccini, Shaowen Jiang, Carolina Alcantara Hirsch, Arnaldo A. Arbini, Warren L. Wu, Harvey Pass, Dafna Bar-Sagi, Thales Papagiannakopoulos, Michele Pagano
Summary: NSCLCs with KEAP1 mutations show resistance to immunotherapy due to EMSY accumulation suppressing immune response. KEAP1 loss results in stabilized EMSY, causing HRR defects and sensitivity to PARP inhibitors. The accumulation of EMSY impairs immune signaling and promotes immune evasion. Activation of the type I interferon response using a STING agonist inhibits KEAP1-mutant tumor growth, suggesting a potential therapeutic strategy for NSCLC patients with KEAP1 alterations.
Article
Oncology
Emma Kurz, Carolina Alcantara Hirsch, Tanner Dalton, Sorin Alberto Shadaloey, Alireza Khodadadi-Jamayran, George Miller, Sumedha Pareek, Hajar Rajaei, Chirayu Mohindroo, Seyda Baydogan, An Ngo-Huang, Nathan Parker, Matthew H. G. Katz, Maria Petzel, Emily Vucic, Florencia McAllister, Keri Schadler, Rafael Winograd, Dafna Bar-Sagi
Summary: Aerobic exercise reduces the growth of pancreatic ductal adenocarcinoma (PDA) by modulating the immune system. It promotes the accumulation of tumor-infiltrating immune cells and enhances the tumor-protective effects. In clinical samples, an increase of anti-tumor immune cells is observed. Targeting the IL-15/IL-15R alpha pathway shows promising results in treatment.
Article
Multidisciplinary Sciences
Madeleine M. LaRue, Seth Parker, Joseph Puccini, Michael Cammer, Alec C. Kimmelman, Dafna Bar-Sagi
Summary: Tumor-associated macrophages play a role in remodeling the extracellular matrix, which affects the growth and development of tumors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Endocrinology & Metabolism
Javier Garcia-Bermudez, Michael A. Badgley, Sheela Prasad, Lou Baudrier, Yuyang Liu, Konnor La, Mariluz Soula, Robert T. Williams, Norihiro Yamaguchi, Rosa F. Hwang, Laura J. Taylor, Elisa de Stanchina, Bety Rostandy, Hanan Alwaseem, Henrik Molina, Dafna Bar-Sagi, Kivanc Birsoy
Summary: This study reveals that pancreatic tumor cells overcome aspartate limitation in hypoxia by upregulating macropinocytosis.
Review
Oncology
Joseph Puccini, Michael Alexander Badgley, Dafna Bar-Sagi
Summary: This review discusses the recent advances in understanding macropinocytosis, including its regulatory pathways, its contribution to the metabolic fitness of cancer cells, and its therapeutic potential.