Article
Biochemical Research Methods
Alexander J. Bryer, Tyler Reddy, Edward Lyman, Juan R. Perilla
Summary: Enveloped viruses are protected by a lipid membrane, and the complex lipid composition of the envelope is closely related to its structural, mechanical, and dynamical properties.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Yu-Chen Yen, Christopher T. Schafer, Martin Gustaysson, Stefanie A. Eberle, Pawel K. Dominik, Dawid Deneka, Penglie Zhang, Thomas J. Schall, Anthony A. Kossiakoff, John J. G. Tesmer, Tracy M. Handel
Summary: This study presents cryo-EM structures of ACKR3 in complex with CXCL12, a more potent CXCL12 variant, and a small-molecule agonist. The binding poses of these chemokines are different from those established for CXCR4 and observed in other receptor-chemokine complexes. These structures, together with functional studies, provide insights into the ligand-binding promiscuity of ACKR3, its inability to couple to G proteins, and its bias towards beta-arrestin, laying the foundation for understanding the physiological interplay of ACKR3 with other GPCRs.
Review
Virology
Pablo Guardado-Calvo, Felix A. Rey
Summary: The fusion of viral and cell lipid bilayers is a key step in the entry of enveloped viruses into cells, driven by a dedicated membrane fusion protein located on the virion surface. Class II fusion machinery consists of two glycoproteins that fold together in the ER of infected cells to avoid premature fusion. Despite diverging in 3D fold during evolution, class II accompanying proteins also derive from a common ancestor and play different functional roles.
Article
Chemistry, Analytical
Peng He, Shannon Faris, Reddy Sudheer Sagabala, Payel Datta, Zihan Xu, Brian Callahan, Chunyu Wang, Benoit Boivin, Fuming Zhang, Robert J. Linhardt
Summary: Cholesterol, an important lipid in animal cell membranes, can bind to various soluble proteins, transport proteins, and membrane-bound proteins. However, studying the interactions between cholesterol and proteins in aqueous solutions is challenging due to the low solubility of cholesterol, often necessitating the use of organic co-solvents or surfactant additives. In this study, a biotinylated cholesterol derivative was synthesized and immobilized on a streptavidin chip for analysis using surface plasmon resonance (SPR). The kinetics of cholesterol interactions with cholesterol-binding proteins, hedgehog protein and tyrosine phosphatase 1B, were determined.
Article
Cell Biology
Daniel Crosby, Melissa R. Mikolaj, Sarah B. Nyenhuis, Samantha Bryce, Jenny E. Hinshaw, Tina H. Lee
Summary: ER network formation depends on membrane fusion by the atlastin (ATL) GTPase. Successful reconstitution of fusion activity by the human ATLs has been achieved. The major splice isoforms of ATL1 and ATL2 are found to be autoinhibited to different degrees. Autoinhibition can be relieved by charge reversal of residues in the inhibitory domain, leading to activation of fusion activity. Neurons express an ATL2 splice isoform with full fusion activity due to sequence differences in the inhibitory domain. These findings highlight the importance of autoinhibition and alternate splicing in regulating atlastin-mediated ER fusion.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Ying Liu, Piyumi Wijesekara, Sriram Kumar, Weitao Wang, Xi Ren, Rebecca E. Taylor
Summary: Structural DNA nanotechnology can guide and affix biomolecules to cell surfaces through targeted binding, with the efficiency highly dependent on the shape of DNA origami and the location of binding overhangs. Edge-decorated nanotiles showed successful labeling of cells, and modulating the labeling efficiency can be achieved by adjusting the proximity of binding overhangs towards the edges and vertices. The findings provide guidelines for rational design of future functional DNA nanostructures.
Article
Biochemistry & Molecular Biology
Ying Huang, Sanchari Sicar, Juan S. Ramirez-Prado, Deborah Manza-Mianza, Javier Antunez-Sanchez, Rim Brik-Chaouche, Natalia Y. Rodriguez-Granados, Jing An, Catherine Bergounioux, Magdy M. Mahfouz, Heribert Hirt, Martin Crespi, Lorenzo Concia, Fredy Barneche, Simon Amiard, Aline Probst, Jose Gutierrez-Marcos, Federico Ariel, Cecile Raynaud, David Latrasse, Moussa Benhamed
Summary: The study reveals the crucial role of H3K27me3 in regulating chromatin interactions in plants, showing that reducing H3K27me3 levels can lead to a global reconfiguration of chromatin architecture and impact gene transcription. These findings highlight the tight link between 3D genome organization and reversible histone modifications in governing chromatin interactions.
Article
Cell Biology
Abigail E. Stanton, Frederick M. Hughson
Summary: The fidelity of vesicle-mediated intracellular transport is crucial for the compartmentalization of eukaryotic cells. This process requires the cooperation of membrane tethers, Sec1/Munc18 (SM) proteins, and SNAREs for efficient and accurate membrane fusion. Recent progress in studying intact multisubunit tethers and their interaction with SNAREs or SM proteins has provided insights into the mechanisms underlying their cooperative action.
CURRENT OPINION IN CELL BIOLOGY
(2023)
Article
Chemistry, Medicinal
David R. Bell, Serena H. Chen
Summary: By using Gaussian process regression, we can accurately predict the impact of point mutations on peptide-MHC class II binding affinity, thus aiding in accelerating the design of antigen-specific immunotherapies.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Biochemistry & Molecular Biology
Carmen Paulmann, Ria Spallek, Oleksandra Karpiuk, Michael Heider, Isabell Schaeffer, Jana Zecha, Susan Klaeger, Michaela Walzik, Rupert Oellinger, Thomas Engleitner, Matthias Wirth, Ulrich Keller, Jan Kroenke, Martina Rudelius, Susanne Kossatz, Roland Rad, Bernhard Kuster, Florian Bassermann
Summary: This study identifies OTUD6B as a key oncogene in multiple myeloma, which stabilizes LIN28B and drives the G1/S transition. High expression of OTUD6B is associated with disease progression and adverse outcome in multiple myeloma.
Article
Physiology
Madhura Chakraborty, Athul Sivan, Arikta Biswas, Bidisha Sinha
Summary: In this study, we investigated the regulation of fluctuation-tension during myogenesis and the role of the fusogen myomerger. Our findings suggest that low tension and clustered surface-myomerger at the early phase are crucial for fusion and can be disrupted by cholesterol-reducing molecules.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Biochemical Research Methods
Zheng Dai, Brooke D. Huisman, Haoyang Zeng, Brandon Carter, Siddhartha Jain, Michael E. Birnbaum, David K. Gifford
Summary: T cells play a crucial role in immune responses, and a machine learning method was used to optimize peptide presentation by class II MHCs. The study shows that modifying anchor residues can improve peptide binding affinity, as demonstrated in a yeast display assay.
Review
Biochemistry & Molecular Biology
Geraldine Schott, Mariano A. Garcia-Blanco
Summary: Research suggests that RNA-binding proteins play a significant role in vertebrate immunity, with six genes encoding proteins potentially involved in immune function and autoimmune diseases.
Review
Virology
Ivanildo P. Sousa, Carlos A. M. Carvalho, Andre M. O. Gomes
Summary: Cholesterol plays a critical role in alphavirus infection, with its importance varying depending on the stage of the virus life cycle and the type of host. Studies in various cell lines suggest that cholesterol not only affects viral replication, but is also crucial for the structural stability of alphavirus particles.
Article
Biochemistry & Molecular Biology
Juan Manuel Orozco Rodriguez, Hanna P. Wacklin-Knecht, Luke A. Clifton, Oliver Bogojevic, Anna Leung, Giovanna Fragneto, Wolfgang Knecht
Summary: In this study, the interaction between human and Escherichia coli DHODH with ubiquinone in lipid membranes was investigated using neutron reflectometry. The results showed that ubiquinone is located in the center of lipid bilayers, and both DHODHs penetrate into the outer lipid leaflet towards ubiquinone. The study also highlighted the importance of ubiquinone and lipid composition in enzyme binding.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Minrui Fan, Jinru Zhang, Chen-Wei Tsai, Benjamin J. Orlando, Madison Rodriguez, Yan Xu, Maofu Liao, Ming-Feng Tsai, Liang Feng
Article
Multidisciplinary Sciences
Benjamin J. Orlando, Maofu Liao
NATURE COMMUNICATIONS
(2020)
Editorial Material
Virology
Pratyush Kumar Das, Margaret Kielian
JOURNAL OF VIROLOGY
(2021)
Review
Physiology
Ashlee M. Plummer, Alan T. Culbertson, Maofu Liao
Summary: Cholesterol homeostasis and trafficking are crucial for maintaining the asymmetric plasma membrane of eukaryotic cells, and disruptions in cholesterol trafficking can lead to various human diseases. ABC transporters, such as ABCA1 and ABCG5/G8, play key roles in this process, with mutations in these proteins linked to disorders like Tangier disease and sitosterolemia. These two proteins function in the reverse cholesterol transport pathway, mediating the efflux of cholesterol and xenosterols to high-density lipoprotein and bile salt micelles, highlighting the importance of understanding sterol transport driven by ABC transporters.
ANNUAL REVIEW OF PHYSIOLOGY, VOL 83
(2021)
Review
Virology
Pratyush Kumar Das, Margaret Kielian
Summary: Rubella virus is an airborne pathogen that can cause miscarriage or congenital rubella syndrome in pregnant women. Vaccination campaigns have reduced infections, but low vaccination coverage countries still face challenges. Studies have increased understanding of the virus, highlighting potential spillover from other mammals and proposing its use as a model for studying more pathogenic viruses.
JOURNAL OF VIROLOGY
(2021)
Article
Multidisciplinary Sciences
Francois A. Thelot, Wenyi Zhang, KangKang Song, Chen Xu, Jing Huang, Maofu Liao
Summary: This study reveals that two inhibitors of the MsbA transporter, TBT1 and G247, have divergent mechanisms of action, inducing inward folding and inward opening states of the protein structure, providing important insights into ABC transporter pharmacology.
Article
Virology
Rebecca S. Brown, Lisa Kim, Margaret Kielian
Summary: Alphaviruses require specific binding of their Capsid protein to genomic RNA for virus assembly, a stem-loop structure on the RNA is identified to facilitate this binding, which is conserved among related alphaviruses such as chikungunya virus and Ross River virus.
Article
Virology
Peiqi Yin, Margaret Kielian
Summary: The study shows significant differences in CHIKV infection between two BHK-21 cell clones, with the expression level of MXRA8 receptor possibly being the underlying cause of this discrepancy.
Article
Multidisciplinary Sciences
Stuti Sharma, Ruoyu Zhou, Li Wan, Shan Feng, KangKang Song, Chen Xu, Yanyan Li, Maofu Liao
Summary: Lipoproteins play a crucial role in bacterial growth and antibiotic resistance. The study reveals the mechanism of how LolCDE recognizes its substrate and the key role of the amide-linked acyl chain in this process. Nucleotide binding triggers large-scale, asymmetric movements in the structure of LolCDE, leading to extrusion of the captured lipoprotein. Comparisons with MacB highlight the conserved mechanism of type VII ABC transporters and the unique properties of LolCDE as a molecule extruder of triacylated lipoproteins.
NATURE COMMUNICATIONS
(2021)
Article
Virology
Bruno A. Rodriguez-Rodriguez, Maria G. Noval, Maria E. Kaczmarek, Kyung Ku Jang, Sara A. Thannickal, Angelica Cifuentes Kottkamp, Rebecca S. Brown, Margaret Kielian, Ken Cadwell, Kenneth A. Stapleford
Summary: The study identified atovaquone and berberine chloride as potential antiviral compounds against SARS-CoV-2, highlighting the importance of proactive approaches in drug development to block emerging viruses before they cause pandemics.
Article
Biochemical Research Methods
Di Liu, Francois A. Thelot, Joseph A. Piccirilli, Maofu Liao, Peng Yin
Summary: This study presents a nanoarchitectural engineering strategy, called ROCK, which enables efficient structural determination of RNA using cryo-EM. By installing kissing-loop sequences onto RNAs, ROCK allows for better self-assembly and higher resolution reconstruction. The application of ROCK to different RNA structures demonstrates its potential in enabling high-quality cryo-EM studies.
Article
Biochemistry & Molecular Biology
Henning Arlt, Xuewu Sui, Brayden Folger, Carson Adams, Xiao Chen, Roman Remme, Fred A. Hamprecht, Frank DiMaio, Maofu Liao, Joel M. Goodman, Robert V. Farese, Tobias C. Walther
Summary: This study reports the structure of yeast seipin and suggests that it forms a flexible, cage-like structure in the endoplasmic reticulum membrane, facilitating lipid droplet formation and growth.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Virology
Kamini Singh, Maria Guadalupe Martinez, Jianan Lin, James Gregory, Trang Uyen Nguyen, Rawan Abdelaal, Kristy Kang, Kristen Brennand, Arnold Grunweller, Zhengqing Ouyang, Hemali Phatnani, Margaret Kielian, Hans-Guido Wendel
Summary: This study used RNA sequencing and ribosome footprinting to investigate the transcriptional and translational dynamics of ZIKV and DENV infections in human neuronal progenitor cells, highlighting cellular stress responses and activation of RNA translation and polyamine metabolism.
Article
Biochemistry & Molecular Biology
Ashlee M. Plummer-Medeiros, Alan T. Culbertson, Claudio L. Morales-Perez, Maofu Liao
Summary: The human ATP-binding cassette transporter ABCA1 plays a critical role in lipid homeostasis. Deleterious mutations of ABCA1 lead to sterol accumulation and are associated with various diseases. The mechanism by which ABCA1 drives lipid movement is poorly understood. In this study, a stable expression system was established for both a human cell-based sterol export assay and protein purification. The produced ABCA1 protein showed activity in sterol export and displayed enhanced ATPase activity. Cryo-EM study revealed multiple distinct conformations and a previously unknown structure of nanodisc-embedded ABCA1. This platform provides important mechanistic and structural insights for investigating ABCA1 modulators.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Xuewu Sui, Kun Wang, Kangkang Song, Chen Xu, Jiunn Song, Chia-Wei Lee, Maofu Liao, Robert V. Farese, Tobias C. Walther
Summary: This study reports the structures of inhibitors of the triacylglycerol synthesis enzyme. The inhibitors were found to block the enzyme's activity by either blocking the entrance of the substrate binding tunnel or interacting with the catalytic residues. Furthermore, the inhibitors showed minimal activity against related enzymes, but a single-residue mutation increased their inhibitory effect.
NATURE COMMUNICATIONS
(2023)