Article
Chemistry, Physical
Wojciech J. Nawrocki, Michael R. Jones, Raoul N. Frese, Roberta Croce, Vincent M. Friebe
Summary: Photosynthetic reaction centers play a crucial role in solar energy conversion, but transferring them from their natural membrane environment to artificial architectures leads to efficiency losses. This study identified bottlenecks in electron transfer and a short-circuiting of separated charges as the main causes for efficiency reduction in a biophotoelectrode.
Article
Biology
William N. Zagotta, Brandon S. Sim, Anthony K. Nhim, Marium M. Raza, Eric G. B. Evans, Yarra Venkatesh, Chloe M. Jones, Ryan A. Mehl, E. James Petersson, Sharona E. Gordon
Summary: With the recent explosion in high-resolution protein structures, there is a new frontier in biology to elucidate the mechanisms of conformational rearrangements in proteins to meet the changing needs of cells. By rigorously measuring protein energetics and dynamics through new methods like tmFRET, differences in conformational states and accurate quantification of distributions can be revealed. This new approach using Acd for time-resolved tmFRET sets the stage for measuring the energetics of conformational rearrangements in soluble and membrane proteins in near-native conditions.
Article
Cell Biology
Mireia Perez Verdaguer, Tian Zhang, Sachin Surve, Joao A. Paulo, Callen Wallace, Simon C. Watkins, Steven P. Gygi, Alexander Sorkin
Summary: This study investigates the endocytosis mechanism of EGFR and its interaction with signaling. By identifying a network of signaling proteins associated with EGFR and demonstrating the role of TFG in endosomal sorting of EGFR, this study opens new avenues for discovering regulatory mechanisms of signaling and intracellular trafficking of receptor tyrosine kinases.
Article
Computer Science, Artificial Intelligence
Yicheng Gao, Yuli Gao, Yuxiao Fan, Chengyu Zhu, Zhiting Wei, Chi Zhou, Guohui Chuai, Qinchang Chen, He Zhang, Qi Liu
Summary: Machine learning methods struggle with antigens for which no or little data exist regarding interactions with the immune system. A new method called PanPep based on meta-learning can learn quickly on new binding prediction tasks and accurately predicts pairing between T-cell receptors and new antigens.
NATURE MACHINE INTELLIGENCE
(2023)
Article
Biochemistry & Molecular Biology
Satomi Adegawa, Naomi Yamaguchi, Ryoichi Sato
Summary: This study investigated the amino acid residues of Cry1Aa toxin involved in binding to Bombyx mori ABC transporter C2, revealing that complex cavities formed by loops alpha 8, 2, and 3 serve as the binding site. Loop swapping experiments indicated that loop 2 plays a critical role in binding affinity generation. Single amino acid substitution mutants demonstrated that Y366, R367, R368, and L447 are important for binding to BmABCC2. Additionally, the study suggested a two-state binding model and highlighted the contribution of complex cavities and specific amino acid residues to multiple binding points and high-affinity binding.
Article
Biochemistry & Molecular Biology
Gouri S. Jas, Ed W. Childs, C. Russell Middaugh, Krzysztof Kuczera
Summary: This study combines time-resolved fluorescence spectroscopy and molecular dynamics simulation to investigate the influence of periodic boundary conditions and water models on the orientation dynamics and diffusion behavior of peptides in solution. The results show that different properties of peptides respond differently to changes in simulation conditions.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemical Research Methods
Iliana Papadopoulou, An-Phi Nguyen, Anna Weber, Maria Rodriguez Martinez
Summary: This study presents a computational pipeline called DECODE that can extract binding rules from black-box models designed to predict TCR-epitope binding. The pipeline can help improve understanding of sequence motifs underlying TCR binding and facilitate research into current immunotherapeutic challenges.
Article
Food Science & Technology
Carla Regina Borges Lopes, Lilia Coronato Courrol
Summary: This study aimed to investigate the impact of packaging materials and storage time on food quality during storage, specifically focusing on photosensitized oxidation in soybean oil. The experiment involved accelerated photo-oxidation with LED in different colored PET packaging and measured the fluorescence spectra and decay curves. The results indicated that transparent PET bottles were ineffective in protecting soybean oil from photosensitized oxidation, and fluorescence parameters were closely correlated with indicators of lipid oxidation progress.
Article
Chemistry, Physical
Noh Soo Han, JunWoo Kim, Tai Hyun Yoon, Minhaeng Cho
Summary: Transient absorption spectroscopy of ThT molecules in various solvents using ASOPS with synchronized femtosecond lasers revealed that vibrational coupling strengths are reduced in chlorine-containing solvents, leading to an increase in fluorescence quantum yield. The study demonstrates the potential of NUV-NUV and NUV-NIR ASOPS techniques for investigating ultrafast photochemical reactions in condensed phases.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Multidisciplinary Sciences
Angela R. Smith, Jesus A. Alonso, Cory M. Ayres, Nishant K. Singh, Lance M. Hellman, Brian M. Baker
Summary: This study shows that modifications at primary anchors, even without structural impact, can significantly affect T cell recognition depending on the TCR. The impact of peptide anchor modification can be sensed by a TCR at regions distant from the modification site, indicating a through-protein mechanism. These findings have implications for the use of anchor-modified peptides and predicting the immunogenicity of tumor neoantigens.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biology
Nadia Fuellbrunn, Zehao Li, Lara Jorde, Christian P. Richter, Rainer Kurre, Lars Langemeyer, Changyuan Yu, Carola Meyer, Jorg Enderlein, Christian Ungermann, Jacob Piehler, Changjiang You
Summary: This study introduces a method called GIET to probe the axial orientation of arrested macromolecules at lipid monolayers, and analyzes the conformational organization of proteins and complexes involved in tethering and fusion at yeast vacuoles. The results reveal that the membrane-anchored Ypt7 protein undergoes conformational reorganization upon interactions with effector proteins, and the tethering complex alternates between 'closed' and 'open' conformations dynamically when recruited to membranes by Ypt7.
Review
Oncology
Robert C. Sterner, Rosalie M. Sterner
Summary: CAR-T cell therapy has shown remarkable clinical responses in certain subsets of leukemia or lymphoma, but faces challenges in solid tumors and hematological malignancies. Innovative strategies and approaches are necessary to overcome these challenges and improve the efficacy of CAR-T cells.
BLOOD CANCER JOURNAL
(2021)
Article
Immunology
Nicole A. Mifsud, Patricia T. Illing, Jeffrey W. Lai, Heidi Fettke, Luca Hensen, Ziyi Huang, Jamie Rossjohn, Julian P. Vivian, Patrick Kwan, Anthony W. Purcell
Summary: This study investigated the impact of antiseizure medications on T cells in patients with Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). The research found that CBZ-reactive memory T cells require both the drug and HLA-B*15:02 for activation, resulting in a focused private TCR profile upon reactivation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Nguyen X. Nguyen, Andrew W. Richens, Linda M. Sircy, Denise E. Allard, Elizabeth M. Kolawole, Brian D. Evavold, Maria Bettini, J. Scott Hale
Summary: The AIM assay is a cytokine-independent technique for identifying Ag-specific T cells based on upregulated expression of activation markers after Ag restimulation. This study analyzed immune responses of TCR-transgenic CD4+ T cells and found that the AIM assay is effective for identifying the frequency of protein immunization-induced effector and memory CD4+ T cells but has limitations in identifying cells induced by viral infection, especially chronic infection. The findings suggest that the AIM assay is a useful tool for quantifying murine Ag-specific CD4+ T cells in protein vaccination.
JOURNAL OF IMMUNOLOGY
(2023)
Article
Allergy
Nicole A. A. Mifsud, Patricia T. T. Illing, Rebecca Ho, Johanna E. E. Tuomisto, Heidi Fettke, Kerry A. A. Mullan, James McCluskey, Jamie Rossjohn, Julian Vivian, Rangsima Reantragoon, Anthony W. W. Purcell
Summary: Allopurinol is a drug used in the treatment of gout but can cause severe and life-threatening hypersensitivity reactions. People carrying the HLA-B*58:01 allotype are at higher risk. The drug metabolite oxypurinol is responsible for T cell-mediated immunopathology, and the TCR repertoire usage of reactive T cells in ALP-induced hypersensitivity reactions has been limitedly studied. This research shows that oxypurinol drives CD8(+) T cell responses and that drug-exposed memory T cells exhibit a proinflammatory immunophenotype. The study also supports the concept of pharmacological interaction with immune receptors and highlights oligoclonal and private clonotypic profiles of OXP-induced TCRs.
Article
Multidisciplinary Sciences
Angela R. Smith, Jesus A. Alonso, Cory M. Ayres, Nishant K. Singh, Lance M. Hellman, Brian M. Baker
Summary: This study shows that modifications at primary anchors, even without structural impact, can significantly affect T cell recognition depending on the TCR. The impact of peptide anchor modification can be sensed by a TCR at regions distant from the modification site, indicating a through-protein mechanism. These findings have implications for the use of anchor-modified peptides and predicting the immunogenicity of tumor neoantigens.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Medicine, Research & Experimental
Cory A. Brennick, Mariam M. George, Marmar M. Moussa, Adam T. Hagymasi, Sahar Al Seesi, Tatiana V. Shcheglova, Ryan P. Englander, Grant L. J. Keller, Jeremy L. Balsbaugh, Brian M. Baker, Andrea Schietinger, Ion I. Mandoiu, Pramod K. Srivastava
Summary: Through an unbiased approach, a large number of effective anticancer neoepitopes have been identified, with properties distinct from conventional epitopes, offering potential for the development of personalized human cancer vaccines.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Biochemistry & Molecular Biology
Jesus A. Alonso, Angela R. Smith, Brian M. Baker
Summary: T cell functional responses generally correlate with the TCR affinity for a peptide/MHC complex, but outliers exist. In a specific outlier case, the unusual behavior was attributed to the use of a position 2 anchor-modified peptide variant instead of the wild type antigen. This study highlights the importance of considering the differences between modified peptides and wild type antigens when selecting TCRs for immunotherapy.
MOLECULAR IMMUNOLOGY
(2021)
Article
Cell Biology
Clarety Kaseke, Ryan J. Park, Nishant K. Singh, Dylan Koundakjian, Arman Bashirova, Wilfredo F. Garcia Beltran, Overbeck C. Takou Mbah, Jiaqi Ma, Fernando Senjobe, Jonathan M. Urbach, Anusha Nathan, Elizabeth J. Rossin, Rhoda Tano-Menka, Ashok Khatri, Alicja Piechocka-Trocha, Michael T. Waring, Michael E. Birnbaum, Brian M. Baker, Mary Carrington, Bruce D. Walker, Gaurav D. Gaiha
Summary: The study found that immunodominant HIV epitopes increase surface stabilization of HLA class-I molecules compared to subdominant epitopes, and HLA class-I-peptide stability is strongly correlated with overall immunodominance hierarchies. Additionally, HLA alleles associated with HIV protection are preferentially stabilized by epitopes derived from topologically important viral regions.
Article
Multidisciplinary Sciences
Hakimeh Ebrahimi-Nik, Marmar Moussa, Ryan P. Englander, Summit Singhaviranon, Justine Michaux, HuiSong Pak, Hiroko Miyadera, William L. Corwin, Grant L. J. Keller, Adam T. Hagymasi, Tatiana Shcheglova, George Coukos, Brian M. Baker, Ion I. Mandoiu, Michal Bassani-Sternberg, Pramod K. Srivastava
Summary: This study demonstrates that low-affinity MHC I-peptide interactions can also trigger strong T cell response and anti-tumour immunity, despite the canonical concept that high-affinity interactions are essential for immunogenicity. Structural modeling suggests that the increased hydrophobicity of neo-epitope surfaces may contribute to higher TCR reactivity in these non-binding epitopes.
NATURE COMMUNICATIONS
(2021)
Review
Immunology
Cory M. Ayres, Brian M. Baker
Summary: Peptides can impact the dynamic properties of MHC proteins, which in turn have significant implications for the immune system.
CURRENT OPINION IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Aaron M. Rosenberg, Brian M. Baker
Summary: This article reviews the history and recent developments in TCR engineering, including efforts to alter TCR affinity, modulate specificity, and develop novel TCR-based constructs.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Katherine A. Richards, Courtney Lavery, Grant L. J. Keller, Jim Miller, Brian M. Baker, Andrea J. Sant
Summary: In our study on the MHC class II molecule expressed in autoimmunity prone SJL mice, we identified a variant that alters the structure of the molecule and affects its recognition by certain antibodies. Through monoclonal antibody blocking experiments, we found that CD4 T cells primarily interacted with a specific region of the MHC class II molecule. Our results indicate that conformational variability in this region may lead to a CD4 T cell repertoire that deviates from the prototypical docking mode on MHC class II peptide complexes, while maintaining recognition of the peptide.
MOLECULAR IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Smita S. Chandran, Jiaqi Ma, Martin G. Klatt, Friederike Dundar, Chaitanya Bandlamudi, Pedram Razavi, Hannah Y. Wen, Britta Weigelt, Paul Zumbo, Si Ning Fu, Lauren B. Banks, Fei Yi, Enric Vercher, Inaki Etxeberria, Watchain D. Bestman, Arnaud Da Cruz Paula, Ilinca S. Aricescu, Alexander Drilon, Doron Betel, David A. Scheinberg, Brian M. Baker, Christopher A. Klebanoff
Summary: Using a high-throughput platform combining single-cell transcriptomic and T cell receptor sequencing, researchers identified an immunogenic public neoantigen derived from mutant PIK3CA. The study further demonstrated that this neoantigen has therapeutic potential and can induce tumor regression when TCR-engineered T cells are adoptively transferred.
Article
Immunology
Grant L. J. Keller, Laura Weiss, Brian M. Baker
Summary: This study focuses on accurately modeling the structural features of peptides presented by class I MHC proteins. They found that the common strategy of selecting decoys based on lowest energy can lead to significant errors. Instead, they developed a data-driven approach to predict near native decoys with high accuracy.
FRONTIERS IN IMMUNOLOGY
(2022)
News Item
Biochemistry & Molecular Biology
Tatiana J. Rosales, Brian M. Baker
Summary: This research provides new insights into antigen loading onto MHC-I proteins, particularly the 'non-classical' MHC-I protein MR1. It has important implications for fundamental immunology and the development of novel immunotherapies.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Chang Liu, Hong Liu, Moumita Dasgupta, Lance M. Hellman, Xiaogang Zhang, Kai Qu, Hui Xue, Yun Wang, Fenling Fan, Qi Chang, Duo Yu, Linhu Ge, Yu Zhang, Ziyou Cui, Pengbo Zhang, Bradley Heller, Hongbing Zhang, Bingyin Shi, Brian M. Baker, Cheng Liu
Summary: This article describes a novel TCRm-based T cell therapy that shows specificity and safety for hepatocellular carcinoma (HCC). The therapy exhibits potent activity against AFP-positive cancer cell lines in both in vitro and in vivo models without affecting AFP-negative cells. In a human safety assessment, no significant adverse events were observed, and evidence of efficacy was seen. Remarkably, one metastatic HCC patient achieved complete remission after nine months and qualified for a liver transplant.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Nishant K. Singh, Jesus A. Alonso, Jason R. Devlin, Grant L. J. Keller, George Gray, Adarsh K. Chiranjivi, Sara G. Foote, Lauren M. Landau, Alyssa G. Arbuiso, Laura Weiss, Aaron M. Rosenberg, Lance M. Hellman, Michael Nishimura, Brian M. Baker
Summary: The study identified a mismatched TCR with a highly atypical geometry that maintains normal function and specificity, providing insights into the determinants of MHC restriction.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Jiaqi Ma, Cory M. Ayres, Lance M. Hellman, Jason R. Devlin, Brian M. Baker
Summary: Through biochemical and dynamic allostery analysis, this study reveals that the peptide sensitivity of the inhibitory murine NK receptor Ly49C arises from small differences in H-2K(b)-binding affinity, driven by peptide-dependent dynamic tuning of electrostatic interactions across the protein-protein interface. A proposed model suggests that different peptides can alter the flexibility of H-2K(b), thus changing the strength of electrostatic interactions and providing a quantitative assessment of how peptides impact Ly49C-binding affinity. This research demonstrates peptide-driven allostery at work in class I MHC proteins and provides insight into how dynamic allostery could affect binding of specific MHC partners.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Cell Biology
Julien Schmidt, Angela R. Smith, Morgane Magnin, Julien Racle, Jason R. Devlin, Sara Bobisse, Julien Cesbron, Victor Bonnet, Santiago J. Carmona, Florian Huber, Giovanni Ciriello, Daniel E. Speiser, Michal Bassani-Sternberg, George Coukos, Brian M. Baker, Alexandre Harari, David Gfeller
Summary: CD8+ T cell recognition of peptide epitopes is crucial in immune responses, but the rules governing which peptides are recognized by T cell receptors remain unclear. Training a predictor called PRIME using recent epitope data improves prediction accuracy, particularly in cancer immunotherapy for identifying new epitopes.
CELL REPORTS MEDICINE
(2021)