Review
Biochemistry & Molecular Biology
Xianni Zhong, Jihui Zhao, Liping Sun
Summary: A whole-cell model is an integrative approach that represents certain aspects of the cell structure and/or function. This review summarizes the workflow of whole-cell modeling into five steps, including gathering information, representing the system into modules, translating input information into scoring function, sampling the whole-cell model, and validating and interpreting the model. By combining available models, the accuracy, precision, and completeness of the integrated cell model can be maximized. The review also discusses the quantitative predictions made by existing whole-cell models and highlights the challenges, future directions, and the opportunity for establishing a community-based integrative spatiotemporal multi-scale whole-cell model.
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
(2022)
Article
Biology
Caitlyn L. McCafferty, Ophelia Papoulas, Mareike A. Jordan, Gabriel Hoogerbrugge, Candice Nichols, Gaia Pigino, David W. Taylor, John B. Wallingford, Edward M. Marcotte
Summary: Intraflagellar transport (IFT) is a crucial process for cargo transport in cilia and is associated with the etiology of genetic diseases. This study combines experimental and computational approaches to determine the overall structure of IFT and provide insights into the pleiotropic nature of ciliopathy-associated genetic variants.
Article
Biochemistry & Molecular Biology
Samantha J. Ziegler, Sam J. B. Mallinson, Peter C. St John, Yannick J. Bomble
Summary: Microorganisms rely on protein interactions for signaling, stimuli response, and growth. Recent developments in structural biology, particularly integrative structural biology, have provided insight into how large protein complexes interact in their native environment. This mini-review discusses the past, present, and potential future of integrative structural biology in characterizing protein interactions in their cellular context.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Review
Biochemistry & Molecular Biology
Xiaoting Tang, Helisa H. Wippel, Juan D. Chavez, James E. Bruce
Summary: Protein structure is crucial for biological functions, and understanding it is fundamental in biological and biomedical research. Crosslinking mass spectrometry is an emerging technique that can capture transient information on protein interactions in their native environment. Combining XL-MS with traditional techniques has the potential to bridge the gap between structural biology and systems biology approaches.
Article
Physics, Fluids & Plasmas
Dhanoj Gupta, Raj Singh, Ryan Ringle, Catherine R. Nicoloff, Igor Rahinov, Oded Heber, Daniel Zajfman
Summary: The simulation technique developed to study space charge interaction in EIBT reveals the significance of space charge in both dispersive and self-bunching regime, affecting trapping efficiency and mass spectrometer performance. The numerical results reproduce experimental data and emphasize the critical importance of considering space charge effects in ion trap dynamics even at low ion density.
Article
Multidisciplinary Sciences
Aneek Banerjee, Sayan Bhakta, Jayati Sengupta
Summary: Cellular factories rely on complex molecular machines to perform key biological functions, with cryogenic electron microscopy playing a crucial role in understanding their mechanisms. By combining time-resolved or mass spectrometry techniques with cryo-EM, additional insights into biological processes can be obtained.
Review
Chemistry, Multidisciplinary
Qingli Zeng, Meng-Chan Xia, Xinchi Yin, Simin Cheng, Zhichao Xue, Siyuan Tan, Xiaoyun Gong, Zihong Ye
Summary: The variation among individual cells has a significant impact on biological functions, and single-cell analysis using mass spectrometry provides unique insights into intricate biochemical mechanisms. However, measuring at the unicellular level is challenging due to the complex composition of cells, small substance quantities, and differences in compound concentrations. Recent advancements in ionization techniques in single-cell mass spectrometry have improved the sensitivity and identification abilities of the method.
FRONTIERS IN CHEMISTRY
(2023)
Article
Chemistry, Analytical
Michael S. Westphall, Kenneth W. Lee, Colin Hemme, Austin Z. Salome, Keaton Mertz, Timothy Grant, Joshua J. Coon
Summary: This article describes an apparatus that can cryogenically land particles from the ion beam of a mass spectrometer onto transmission electron microscope grids for cryo-electron microscopy. This system also allows for the controlled formation of thin films of amorphous ice on the grid surface. The study demonstrates that using this cryogenic landing device significantly improves the structural preservation of deposited protein-protein complexes compared to room temperature landings, and landing under cryogenic conditions can increase the diversity of particle orientations, enabling improved 3D structural interpretation.
ANALYTICAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Xin Ma
Summary: Mass spectrometry (MS) is a central technique used for analyzing molecular structures of unknown compounds in the gas phase. It converts molecules into ions and measures their molecular weights accurately. Tandem MS allows detailed structural characterization by breaking molecules into fragment ions. MS is widely used in multiomics studies to reveal the structures and functions of biomolecules. It is a highly sensitive and versatile technique that can be coupled with other analytical instruments. This review focuses on the technical advances of MS-based structural elucidation methods and their applications in complex mixture analysis.
Article
Biochemistry & Molecular Biology
Daniel S. Ziemianowicz, Jan Kosinski
Summary: Integrative structural modeling is a method that combines data from multiple sources to determine the structures of macromolecules and their complexes. Recent developments in cellular structural biology, such as in-cell cryo-electron tomography and artificial intelligence-based structure prediction, have opened up new opportunities for integrative structural modeling. This review discusses these opportunities, as well as the latest developments in integrative modeling methods and their applications, while also highlighting the challenges and directions for further development.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Wibke Schumann, Jennifer Loschwitz, Jens Reiners, Daniel Degrandi, Larissa Legewie, Kai Stuehler, Klaus Pfeffer, Gereon Poschmann, Sander H. J. Smits, Birgit Strodel
Summary: This study investigates the dimer structures of Guanylate-binding proteins (GBPs) and reveals the differences in protein dynamics and dimerization modes, which are crucial for the GBPs' function in disrupting pathogen membranes.
Article
Biochemistry & Molecular Biology
Wibke Schumann, Jennifer Loschwitz, Jens Reiners, Daniel Degrandi, Larissa Legewie, Kai Stuehler, Klaus Pfeffer, Gereon Poschmann, Sander H. J. Smits, Birgit Strodel
Summary: GBPs are crucial GTPases activated by interferon-gamma, playing an important role in host defense against intracellular bacteria and parasites. This study presents dimer models for human GBP1 and murine GBP2 and GBP7, revealing differences in protein dynamics and dimerization among them.
Review
Biochemistry & Molecular Biology
Rachel Evans, Sravani Ramisetty, Prakash Kulkarni, Keith Weninger
Summary: Intense study of intrinsically disordered proteins (IDPs) began in the late 1990s and revealed their important functions. Over the past two decades, it has become clear that IDPs play critical roles in various biological phenomena. The application of integrative structural biology has emerged as an essential approach to understanding IDP phenomena.
Article
Chemistry, Multidisciplinary
Yao Qian, Xiangyu Guo, Yunfang Wang, Zheng Ouyang, Xiaoxiao Ma
Summary: A mobility-modulated sequential dissociation (MMSD) strategy was developed for mass spectrometry imaging, enabling spatial lipidomics capable of multiplexed MS/MS imaging of 24 structurally distinct lipids. The method revealed a potential biomarker in a human hepatocellular carcinoma tissue.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Multidisciplinary Sciences
Ian C. H. Lee, Sergey Tumanov, Jason W. H. Wong, Roland Stocker, Joshua W. K. Ho
Summary: Mass spectrometry-based untargeted metabolomic and lipidomic approaches are widely used in biomedical research. A sample extraction method called Multi-ABLE has been developed for concurrent generation of proteomic, metabolomic, and lipidomic data. However, there is a lack of a unified bioinformatics pipeline for processing and analysis of these data. A new R pipeline called MultiABLER is presented here as a unified and simple upstream processing and analysis pipeline for metabolomics and lipidomics datasets.
Article
Virology
Esther S. Brielle, Dina Schneidman-Duhovny, Michal Linial
Article
Biochemistry & Molecular Biology
Anne Slavotinek, Doriana Misceo, Stephanie Htun, Linda Mathisen, Eirik Frengen, Michelle Foreman, Jennifer E. Hurtig, Liz Enyenihi, Maria C. Sterrett, Sara W. Leung, Dina Schneidman-Duhovny, Juvianee Estrada-Veras, Jacque L. Duncan, Charlotte A. Haaxma, Erik-Jan Kamsteeg, Vivian Xia, Daniah Beleford, Yue Si, Ganka Douglas, Hans Einar Treidene, Ambro van Hoof, Milo B. Fasken, Anita H. Corbett
HUMAN MOLECULAR GENETICS
(2020)
Article
Chemistry, Multidisciplinary
Esther S. Brielle, Isaiah T. Arkin
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2020)
Article
Genetics & Heredity
Ehud Banne, Tzipora Falik-Zaccai, Esther Brielle, Limor Kalfon, Hagay Ladany, Danielle Klinger, Dina Schneidman-Duhovny, Michal Linial
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
(2020)
Article
Multidisciplinary Sciences
Hannes Braberg, Ignacia Echeverria, Stefan Bohn, Peter Cimermancic, Anthony Shiver, Richard Alexander, Jiewei Xu, Michael Shales, Raghuvar Dronamraju, Shuangying Jiang, Gajendradhar Dwivedi, Derek Bogdanoff, Kaitlin K. Chaung, Ruth Huttenhain, Shuyi Wang, David Mavor, Riccardo Pellarin, Dina Schneidman, Joel S. Bader, James S. Fraser, John Morris, James E. Haber, Brian D. Strahl, Carol A. Gross, Junbiao Dai, Jef D. Boeke, Andrej Sali, Nevan J. Krogan
Article
Multidisciplinary Sciences
Stefan Steimle, Trevor van Eeuwen, Yavuz Ozturk, Hee Jong Kim, Merav Braitbard, Nur Selamoglu, Benjamin A. Garcia, Dina Schneidman-Duhovny, Kenji Murakami, Fevzi Daldal
Summary: Respiratory electron transport complexes in Gram-negative bacteria can be organized as individual entities or combined into large supercomplexes, with specific cytochromes mediating electron transfer. Recent studies have provided insights into the characteristics of membrane-confined and membrane-external respiratory electron transport pathways in these bacteria.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Yufei Xiang, Zhe Sang, Lirane Bitton, Jianquan Xu, Yang Liu, Dina Schneidman-Duhovny, Yi Shi
Summary: This study developed a proteomic strategy to explore the landscape of circulating camelid heavy-chain antibodies, identified a large number of high-affinity nanobody families, analyzed their binding epitopes with antigens, and revealed the mechanism of highly selective binding to specific antigens.
Article
Chemistry, Physical
Esther S. Brielle, Isaiah T. Arkin
Summary: Vibrational spectroscopy is a powerful tool for analyzing biological and chemical samples. Isotope editing, particularly using 1-C-13 = O-16 and 1-C-13 = O-18 labels, has enabled excellent site-specific resolution in characterizing proteins. The introduction of the 1-C-13-N-15 probe along the protein backbone has expanded the vibrational spectroscopy toolkit, providing new molecular insights. The experimentally determined shifts and DFT calculations support the mode assignment, showing the potential for simultaneous use of multiple labeling schemes to enhance detailed molecular insights.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Article
Multidisciplinary Sciences
Dapeng Sun, Zhe Sang, Yong Joon Kim, Yufei Xiang, Tomer Cohen, Anna K. Belford, Alexis Huet, James F. Conway, Ji Sun, Derek J. Taylor, Dina Schneidman-Duhovny, Cheng Zhang, Wei Huang, Yi Shi
Summary: Highly potent neutralizing nanobodies (Nbs) targeting the receptor binding domain (RBD) of the SARS-CoV-2 spike protein show effectiveness against circulating variants of concern. Structural analysis of the Nbs provides insights into their high-affinity and broadly neutralizing activity against the virus.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Zhuolun Shen, Yufei Xiang, Sandra Vergara, Apeng Chen, Zhengyun Xiao, Ulises Santiago, Changzhong Jin, Zhe Sang, Jiadi Luo, Kong Chen, Dina Schneidman-Duhovny, Carlos Camacho, Guillermo Calero, Baoli Hu, Yi Shi
Summary: Researchers developed a Nb-HSA nanobody that can be fused to small biologics to extend half-life, significantly prolonging the half-lives of Nb(HSA)s and finding that their pharmacokinetics positively correlate with their albumin binding affinities at endosomal pH.
Article
Multidisciplinary Sciences
Esther S. Brielle, Jeffrey Fleisher, Stephanie Wynne-Jones, Kendra Sirak, Nasreen Broomandkhoshbacht, Kim Callan, Elizabeth Curtis, Lora Iliev, Ann Marie Lawson, Jonas Oppenheimer, Lijun Qiu, Kristin Stewardson, J. Noah Workman, Fatma Zalzala, George Ayodo, Agness O. Gidna, Angela Kabiru, Amandus Kwekason, Audax Z. P. Mabulla, Fredrick K. Manthi, Emmanuel Ndiema, Christine Ogola, Elizabeth Sawchuk, Lihadh Al-Gazali, Bassam R. Ali, Salma Ben-Salem, Thierry Letellier, Denis Pierron, Chantal Radimilahy, Jean-Aime Rakotoarisoa, Ryan L. Raaum, Brendan J. Culleton, Swapan Mallick, Nadin Rohland, Nick Patterson, Mohammed Ali Mwenje, Khalfan Bini Ahmed, Mohamed Mchulla Mohamed, Sloan R. Williams, Janet Monge, Sibel Kusimba, Mary E. Prendergast, David Reich, Chapurukha M. Kusimba
Summary: The urban peoples of the Swahili coast were early practitioners of Islam and traded with eastern Africa and the Indian Ocean. The study found that many individuals in coastal towns had a mixed ancestry, with more than half of their DNA coming from African female ancestors and a significant portion coming from Asian ancestors, particularly Persian men. The sources of DNA changed over time, with a shift from mainly Persian-related ancestry to Arabian ancestry, indicating increased interactions with southern Arabia.
Article
Multidisciplinary Sciences
Yufei Xiang, Sham Nambulli, Zhengyun Xiao, Heng Liu, Zhe Sang, W. Paul Duprex, Dina Schneidman-Duhovny, Cheng Zhang, Yi Shi