Article
Chemistry, Multidisciplinary
Guangyan Zhou, Li He, Kathy H. Li, Cassio C. S. Pedroso, Miriam Gochin
Summary: The study presented a low molecular weight covalent inhibitor targeting a conserved lysine residue within the hydrophobic pocket of HIV-1 glycoprotein-41, which exhibited significantly enhanced anti-viral activity compared to its non-covalent counterpart. This represents a major advancement in the quest for non-peptide fusion inhibitors.
CHEMICAL COMMUNICATIONS
(2021)
Article
Immunology
Daniel Hatlem, Mikkel Christensen, Nina K. Broeker, Per E. Kristiansen, Reidar Lund, Stefanie Barbirz, Dirk Linke
Summary: Alpha-helical coiled-coils are common protein structures found in all living organisms. Modified coiled-coil sequences have been widely used in biotechnology, vaccine development, and biochemical research to induce protein oligomerization and form self-assembled protein scaffolds. In this study, a trimeric variant of a peptide derived from the yeast transcription factor GCN4, called GCN4-pII, was shown to bind bacterial lipopolysaccharides (LPS) with high affinity. LPS molecules are toxic glycolipids found in the outer membrane of Gram-negative bacteria. The researchers also demonstrated the ability of GCN4-pII to break down LPS micelles in solution. These findings suggest that GCN4-pII and its derivatives could be used for novel LPS detection and removal solutions with important applications in the production and quality control of biopharmaceuticals and other biomedical products, where even trace amounts of residual LPS can be deadly.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Virology
Chao Wang, Qing Li, Lujia Sun, Xinling Wang, Huan Wang, Wenpeng Zhang, Jiahui Li, Yang Liu, Lu Lu, Shibo Jiang
Summary: Researchers developed a novel dual-target inhibitor by integrating a small-molecule HIV-1 inhibitor with an artificial peptide. This inhibitor showed improved activity against multiple drug-resistant HIV-1 strains.
Article
Biochemical Research Methods
Jacobo Gomez-Gonzalez, David Bouzada, Lidia A. Perez-Marquez, Giuseppe Sciortino, Jean-Didier Marechal, Miguel Vazquez Lopez, M. Eugenio Vazquez
Summary: The combination of coordination chemistry and peptide engineering is a promising strategy for developing novel molecular structures. In this study, the beta-annulus motif was found to direct the stereoselective assembly of designed peptides into chiral helicates, which exhibited high affinity for three-way DNA junctions.
BIOCONJUGATE CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Mario Cano-Munoz, Julie Lucas, Li-Yun Lin, Samuele Cesaro, Christiane Moog, Francisco Conejero-Lara
Summary: This study identified the vulnerability of the gp41 C-terminal heptad repeat to inhibition and demonstrated that engineering stable miniproteins can enhance inhibitory potency against HIV-1. These findings have implications in the development of new strategies to inhibit HIV targeting the gp41 CHR region.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Virology
Soohyun Kim, Maria V. Filsinger V. Interrante, Peter S. S. Kim
Summary: The trimeric glycoprotein Env on the surface of HIV-1 is the target of broadly neutralizing antibodies and vaccine development efforts. Antibodies that target the membrane proximal external region (MPER) of Env show lipid-binding characteristics and increasing their local concentration through binding to the Fc receptor Fc gamma RI can potentiate their ability to prevent viral entry. This study shows that lipid-binding activity and Fc gamma RI-mediated potentiation work together to improve the potency of MPER-directed antibodies by increasing their local concentration near the site of viral fusion.
JOURNAL OF VIROLOGY
(2023)
Article
Chemistry, Multidisciplinary
Hermann Neitz, Niels Benjamin Paul, Florian R. Hage, Christina Lindner, Roman Graebner, Michael Kovermann, Franziska Thomas
Summary: The study presents a combinatorial approach to identify novel functional mini-proteins based on the WW-domain scaffold. The WW domain fragments were reconstituted through coiled coil association, and the binding properties were fully restored. Using this approach, specific binding domains for ATP and phosphorylcholine were identified.
Article
Biochemistry & Molecular Biology
Michael D. Jorgensen, Jean Chmielewski
Summary: TriCross is a peptide sequence that can assemble into a stable three-dimensional matrix in the presence of metal ions, encapsulating and releasing cells, making it suitable for 3D cell culture.
JOURNAL OF PEPTIDE SCIENCE
(2022)
Article
Cell Biology
Madeleine F. Jennewein, Anna J. MacCamy, Nicholas R. Akins, Junli Feng, Leah J. Homad, Nicholas K. Hurlburt, Emily Seydoux, Yu-Hsin Wan, Andrew B. Stuart, Venkata Viswanadh Edara, Katharine Floyd, Abigail Vanderheiden, John R. Mascola, Nicole Doria-Rose, Lingshu Wang, Eun Sung Yang, Helen Y. Chu, Jonathan L. Torres, Gabriel Ozorowski, Andrew B. Ward, Rachael E. Whaley, Kristen W. Cohen, Marie Pancera, M. Juliana McElrath, Janet A. Englund, Andres Finzi, Mehul S. Suthar, Andrew T. McGuire, Leonidas Stamatatos
Summary: The study identified 14 neutralizing antibodies against SARS-CoV-2, with 3 able to cross-neutralize SARS-CoV-1. The in vivo protective potential of antibodies is regulated by neutralization potency and epitope specificity. The study also suggests that epitopes in S2 can be used as blueprints for designing immunogens capable of eliciting cross-neutralizing coronavirus antibodies.
Article
Cell Biology
Charles D. Murin, Pavlo Gilchuk, Philipp A. Ilinykh, Kai Huang, Natalia Kuzmina, Xiaoli Shen, Jessica F. Bruhn, Aubrey L. Bryan, Edgar Davidson, Benjamin J. Doranz, Lauren E. Williamson, Jeffrey Copps, Tanwee Alkutkar, Andrew Flyak, Alexander Bukreyev, James E. Crowe, Andrew B. Ward
Summary: This study identified antibodies targeting the glycan cap epitope on the ebolavirus glycoprotein with broad neutralizing activity, and revealed the structural features of these antibodies working in synergy with base-binding antibodies. The study provides a molecular basis for ebolavirus neutralization by broadly reactive glycan cap antibodies.
Article
Biophysics
Yonglan Liu, Hyunbum Jang, Mingzhen Zhang, Chung-Jung Tsai, Ryan Maloney, Ruth Nussinov
Summary: This study provides insights into the molecular mechanism of BCR-ABL recruitment of GRB2, revealing the determinants of specificity in the recognition between SH2(GRB2) and phosphorylated BCR. The findings contribute to the prediction of BCR-binding scaffolds and the design of therapeutic peptides.
BIOPHYSICAL JOURNAL
(2022)
Review
Biochemical Research Methods
Christopher J. Addonizio, Brant D. Gates, Matthew J. Webber
Summary: The fields of precision imaging and drug delivery have introduced various tools to enhance target specificity and efficacy in diagnosing and treating diseases. Biological molecules and molecular recognition motifs play key roles in ensuring active targeting and specificity, while bioorthogonal covalent conjugations and supramolecular motifs offer possibilities for in situ complexation under physiological conditions.
BIOCONJUGATE CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Gage O. Leighton, Elizabeth Marie Irvin, Parminder Kaur, Ming Liu, Changjiang You, Dhruv Bhattaram, Jacob Piehler, Robert Riehn, Hong Wang, Hai Pan, David C. Williams
Summary: This study investigates the binding and diffusion characteristics of MBD2 and MBD3 on different DNA templates using single-molecule and biophysical analyses. The results show that both MBD2 and MBD3 can freely diffuse across unmethylated CpG-rich DNA, but methylation of large CpG islands traps MBD2 while MBD3 continues to diffuse freely. Additionally, both proteins bend DNA, with methylation augmenting this effect.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Ashley E. Modell, Frank Marrone, Nihar R. Panigrahi, Yingkai Zhang, Paramjit S. Arora
Summary: Constrained peptides are a valuable source of ligands for protein surfaces, but their binding affinity is often limited. This study proposes the use of nonnatural side chains to enhance binding affinity by accessing unoccupied crevices on the receptor surface. The computational method, AlphaSpace, was used to predict peptide ligands for the KIX domain of the p300/CBP coactivator, and experimental screening was performed to fine-tune the nonnatural side chains. The combined computational-experimental approach offers a general framework for optimizing peptidomimetics as inhibitors of protein-protein interactions.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Cell Biology
Ennio A. D'Amico, Misbha Ud Din Ahmad, Verena Cmentowski, Mathias Girbig, Franziska Mueller, Sabine Wohlgemuth, Andreas Brockmeyer, Stefano Maffini, Petra Janning, Ingrid R. Vetter, Andrew P. Carter, Anastassis Perrakis, Andrea Musacchio
Summary: The study provides a structure-function analysis of the Spindly protein, revealing its auto-inhibition mechanism and activation process. The researchers discovered that Spindly is activated by binding to two distinct kinetochore triggers, leading to conformational changes that unleash its Dynein-Dynactin adaptor activity. This study sheds light on the specific activation of Dynein at defined cellular locales.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Thomas Schmidt, Jaekyun Jeon, Wai-Ming Yau, Charles D. Schwieters, Robert Tycko, G. Marius Clore
Summary: Recent advances in rapid mixing and freeze quenching have allowed for the study of protein-substrate interactions using time-resolved electron paramagnetic resonance (EPR)-based double electron-electron resonance (DEER) and solid-state NMR. These methods provide valuable information on the kinetic and structural pathways of protein-substrate binding.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Jiadong Sun, Gengxiang Zhao, Tatsiana Bylund, Myungjin Lee, Srikar Adibhatla, Peter D. Kwong, Gwo-Yu Chuang, Reda Rawi, Carole A. Bewley
Summary: Lectins, such as the therapeutic lectin griffithsin (GRFT), have the potential to bind to carbohydrates and glycan shields, making them promising for therapeutic and diagnostic applications. By studying the structure and activity of GRFT, researchers have identified a critical core structure that is important for antiviral activity and binding to high mannose glycans. This discovery may help in designing carbohydrate receptors and improving the affinity and stability of known lectins.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biology
Nashaat T. Nashed, Annie Aniana, Rodolfo Ghirlando, Sai Chaitanya Chiliveri, John M. Louis
Summary: This study assesses the impact of dimer formation on the catalytic activity of SARS-CoV-2 main protease. The results show that the addition of an inhibitor can increase the catalytic activity, but too high concentrations can decrease the activity. These findings reveal the correlation between dimer formation and enzymatic activity, providing a strategy for designing new drugs.
COMMUNICATIONS BIOLOGY
(2022)
Review
Cell Biology
G. Marius Clore
Summary: Solution nuclear magnetic resonance (NMR) spectroscopy is a powerful technique for analyzing three-dimensional structure and dynamics of macromolecules at atomic resolution. Recent advances in NMR have allowed the detection and characterization of transient states of biological macromolecules, which play key roles in various biological processes. This study demonstrates the application of NMR techniques in unraveling the complex mechanism of sub-millisecond oligomerization and the inhibition of fibril formation in huntingtin.
JOURNAL OF CELL SCIENCE
(2022)
Article
Chemistry, Physical
Alberto Ceccon, Nina Kubatova, John M. Louis, G. Marius Clore, Vitali Tugarinov
Summary: The global motions of ubiquitin on the surface of bicelles were studied. Ubiquitin undergoes internal rotation on the bicelle surface, while the rotation axis wobbles in a cone motion.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Chemistry, Multidisciplinary
Thomas Schmidt, David Wang, Jaekyun Jeon, Charles D. Schwieters, G. Marius Clore
Summary: The study demonstrates the existence of substates of calcium-loaded calmodulin that can be trapped and analyzed experimentally, revealing a complex energy landscape with varying proportions and characteristics of different structural states.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biology
Nashaat T. Nashed, Daniel W. Kneller, Leighton Coates, Rodolfo Ghirlando, Annie Aniana, Andrey Kovalevsky, John M. Louis
Summary: This study investigates the structural characterization and catalytic activity of SARS-Cov-2 main protease, revealing that inhibitor-induced conformational changes of the oxyanion loop are key to dimer formation. Mass spectrometry and crystal structure analysis demonstrate the modulatory role of structural changes in autoprocessing of the main protease.
COMMUNICATIONS BIOLOGY
(2022)
Review
Chemistry, Multidisciplinary
Carole A. Bewley, Gary A. Sulikowski, Zhongyue J. Yang, Giuseppe Bifulco, Hyo-Moon Cho, Christopher R. Fullenkamp
Summary: Natural products, produced by enzymatic assembly lines, have played a crucial role in the discovery of antibiotics, antineoplastics, and therapeutics. They have unique three-dimensional shapes and stereochemistry, which determine their diverse functions and biological activities. With advancements in methods and tools, research on atropisomerism in natural products and related scaffolds is progressing.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Article
Chemistry, Physical
Vitali Tugarinov, Yusuke Okuno, Francesco Torricella, Theodoros K. Karamanos, G. Marius Clore
Summary: Degenerate spin systems are challenging for CPMG relaxation dispersion NMR experiments. A simple alternative method called the steady-state CPMG scheme is proposed, which utilizes acute-angle 1H radiofrequency pulses to establish a steady-state for effective rates of magnetization decay. The method is applied to two protein systems with different exchange regimes.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Multidisciplinary
Yusuke Okuno, Charles D. Schwieters, Zhilin Yang, G. Marius Clore
Summary: This study explores distinct properties of solvent paramagnetic relaxation enhancement (sPRE) arising from nitroxide-based cosolutes and provides new insights into the interpretation of sPRE and sPRE-derived OENS. Four different approaches for evaluating OENS are discussed, which enable the investigation of both long-range and short-range electrostatic interactions.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Mengli Cai, Vitali Tugarinov, Sai Chaitanya Chiliveri, Ying Huang, Charles D. Schwieters, Kyoshi Mizuuchi, G. Marius Clore
Summary: The bacterial MinE and MinD division regulatory proteins form a standing wave enabling MinC, which binds MinD, to inhibit FtsZ polymerization except at the midcell. The structure and dynamics of MinE bound to disc-shaped lipid bicelles are probed using NMR. In the bicelle-bound state, helix alpha 1 interacts with the bicelle surface, while the protein core remains unperturbed and also interacts with the bicelle surface via helix alpha 2. The results provide insights into MinE structural rearrangements during bacterial cell division.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Shreya Ghosh, Vitali Tugarinov, G. Marius Clore
Summary: The chaperone Hsp104 prevents fibril formation of amyloidogenic peptides in a substochiometric manner. By studying its interaction with the A(342) peptide, it was found that Hsp104 binds reversibly to sparsely populated nuclei of A(342), completely inhibiting fibril formation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Physical
Yusuke Okuno, G. Marius Clore
Summary: This paper shows that it is possible to extend the frequency range of solvent paramagnetic relaxation enhancement (sPRE) experiments by acquiring data at different temperatures. By using the scaling property of spectral densities, the authors were able to accurately calculate the energy and timescale of cosolute-protein interactions. The effective near-surface potentials obtained from this method provide reliable measures of intermolecular interactions.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Multidisciplinary Sciences
Alberto Ceccon, Vitali Tugarinov, Francesco Torricella, G. Marius Clore
Summary: The tetramerization of the N-terminal region of the huntingtin protein is crucial for the development of Huntington's disease, and fibril formation occurs through nucleation and elongation processes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)