Review
Physiology
Jay M. Baraban, Eric Tuday, Dan E. Berkowitz, Sam Das
Summary: Research suggests that microRNA may play a key role in regulating vascular structure and function, potentially impacting arterial stiffness. In particular, inhibiting a specific enzyme involved in microRNA degradation can reverse aging-associated arterial stiffening, offering potential new strategies for combating this condition in the future.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Cell Biology
Vinayaki Pillai, Alka Gupta, A. V. S. S. N. Rao, Rajani Kant Chittela
Summary: In this study, we characterized ten clinically relevant variants of human Translin protein and found that these variants can modulate the RNase activity of the protein without altering its DNA-dependent function.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Article
Peripheral Vascular Disease
Eric Tuday, Mitsunori Nakano, Kei Akiyoshi, Xiuping Fu, Aparna P. Shah, Atsushi Yamaguchi, Charles Steenbergen, Lakshmi Santhanam, Steven S. An, Dan Berkowitz, Jay M. Baraban, Samarjit Das
Summary: This study reveals the crucial role of miR-181b in mediating arterial stiffness by regulating the stiffness of vascular smooth muscle cells (VSMCs), as well as the involvement of TN/TX RNase activity in this process. It suggests that therapeutic strategies targeting TN/TX-mediated reductions in miR-181b levels may provide protection against cardiovascular diseases related to large artery stiffness.
Article
Biochemistry & Molecular Biology
Roslin J. Adamson, N. Connor Payne, Sergio G. Bartual, Ralph Mazitschek, Alex N. Bullock
Summary: KEAP1 promotes the ubiquitin-dependent degradation of NRF2 by assembling into a CUL3-dependent ubiquitin ligase complex. Oxidative and electrophilic stress inhibit KEAP1, allowing NRF2 to accumulate for stress response gene transactivation. The crystal structure of the BTB and 3-box domains of human KEAP1 in complex with the CUL3 N-terminal domain revealed a heterotetrameric assembly with 2:2 stoichiometry. The developed TRFRET-based assay system and binding profile data provide valuable insights into the KEAP1-CUL3 interaction.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Likui Zhang, Lei Wang, Leilei Wu, Donghao Jiang, Chengxuan Tang, Ying Wu, Mai Wu, Min Chen
Summary: Endonuclease III (EndoIII) from the hyperthermophilic crenarchaeon Sulfolobus islandicus REY15A is capable of removing Tg from DNA at high temperature, with optimal temperature and pH at around 70 degrees C and 7.0-8.0, respectively. It is a bifunctional enzyme with glycosylase and AP lyase activities, and forms a covalent intermediate with Tg-containing dsDNA, with specific residues responsible for its catalytic functions.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Michael Schmitz, Irma Querques, Seraina Oberli, Christelle Chanez, Martin Jinek
Summary: This study uncovers the key mechanistic aspects underlying RNA-mediated assembly of CRISPR-associated transposons and their development as programmable tools for site-specific insertion of large DNA payloads.
Article
Biochemistry & Molecular Biology
Yashwanth Ashok, Carlos Vela-Rodriguez, Chunsong Yang, Heli I. Alanen, Fan Liu, Bryce M. Paschal, Lari Lehtio
Summary: This study provides insights into the mechanism of ADP-ribosylation and ubiquitination mediated by DTX3L-PARP9 through intra- and inter-subunit interactions.
BIOCHEMICAL JOURNAL
(2022)
Article
Multidisciplinary Sciences
Han Seong Kim, Dong-wook Kim, Sungjin Kim, Sunghwa Choe
Summary: The study found that mgCas12a proteins have the potential to be used in biotechnological applications, comparable to Cas9 or even better. Compared to Cas9, mgCas12a proteins have higher purification yield and lower non-specific nuclease activity, making them more versatile.
SCIENTIFIC REPORTS
(2022)
Review
Immunology
Marissa L. Matsumoto
Summary: As central effectors of the adaptive immune response, immunoglobulins, or antibodies, provide essential protection from pathogens. IgA and IgM, the only antibody isotypes capable of multimerization, have unique biological functions and play critical roles in mucosal immunity.
ANNUAL REVIEW OF IMMUNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Chengxuan Tang, Donghao Jiang, Likui Zhang
Summary: In this study, we characterized an EndoIII enzyme from a hyperthermophilic archaeon and demonstrated its ability to excise Tg from DNA. We also found that this enzyme has unique thermostability and salt requirement compared to other archaeal EndoIII homologues. Our study provides insights into the additional function and catalytic mechanism of archaeal EndoIII.
WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Mateusz Manicki, Halil Aydin, Luciano A. Abriata, Katherine A. Overmyer, Rachel M. Guerra, Joshua J. Coon, Matteo Dal Peraro, Adam Frost, David J. Pagliarini
Summary: This study presents structure-function analyses of a complex comprising COQ7 and COQ9, revealing their roles in the synthesis of CoQ. The findings suggest that COQ7 and COQ9 interact to form a complex that facilitates the translocation of CoQ intermediates from the membrane to the protein's lipid-binding sites.
Article
Genetics & Heredity
Mai Wu, Guangyu Ma, Yushan Lin, Philippe Oger, Peng Cao, Likui Zhang
Summary: This study reveals the biochemical characteristics of EndoQ from Thermococcus gammatolerans and the roles of its conserved residues in DNA cleavage. The enzyme is highly efficient in cleaving DNA with deaminated bases, especially uracil-containing DNA. It displays the maximum activity at high temperature and neutral to slightly alkaline pH, and it is extremely thermostable. Mutational analysis identifies essential and catalytic residues in the enzyme.
Article
Biochemistry & Molecular Biology
Ingie Elchennawi, Philippe Carpentier, Christelle Caux, Marine Ponge, Sandrine Ollagnier de Choudens
Summary: Iron-sulfur (Fe-S) clusters are essential for cellular pathways and require proteins to mobilize sulfur and iron for their assembly. The SUF system in Mycobacterium tuberculosis is the primary Fe-S biogenesis system and a potential target for fighting tuberculosis. In this study, two proteins of the Mtb SUF system, Rv1464(sufS) and Rv1465(sufU), were characterized and their interaction and activities in Fe-S biogenesis were investigated.
Review
Biochemistry & Molecular Biology
Kavan Gor, Olivier Duss
Summary: Ribosome assembly is a crucial process in gene expression, and studying its molecular mechanisms has led to the development of novel approaches for investigating the assembly of other RNA-protein complexes. This review discusses biochemical, structural, and biophysical methods that have been used to understand the complex process of bacterial ribosome assembly. It also explores emerging approaches for studying how transcription, RNA processing, cellular factors, and the cellular environment influence ribosome and RNA-protein complex assembly.
Review
Biochemistry & Molecular Biology
Xingchen Xiong, Zhiwen Lu, Lixin Ma, Chao Zhai
Summary: Programmable endonucleases, such as Cas and pAgo, can recognize and cleave DNA sequences at nearly any arbitrary site by base pairing with guide RNA or DNA. This review focuses on the use of these enzymes in in vivo and in vitro recombination-based gene cloning methods, and the advantages and disadvantages of using programmable endonucleases for gene cloning are discussed.
Article
Chemistry, Medicinal
Ah Young Park, Imane Nafia, Damien N. Stringer, Samuel S. Karpiniec, J. Helen Fitton
Summary: Fucoidan compounds were found to promote proliferation and activity of immune cells and enhance the effects of the immune-checkpoint inhibitor drug Nivolumab. Additionally, these compounds directly inhibited the growth of prostate cancer cells but did not increase their cell killing activity.
Article
Multidisciplinary Sciences
Siyun Chen, Tamar Getter, David Salom, Di Wu, Daniel Quetschlich, Dror S. Chorev, Krzysztof Palczewski, Carol V. Robinson
Summary: This study investigated the signalling events of G protein-coupled receptors (GPCRs) using mass spectrometry in native membranes. The findings revealed the role of native lipids in rhodopsin signalling and regeneration, and proposed a paradigm for GPCR drug discovery in native membrane environments.
Article
Multidisciplinary Sciences
Abraham O. Oluwole, Robin A. Corey, Chelsea M. Brown, Victor M. Hernandez-Rocamora, Phillip J. Stansfeld, Waldemar Vollmer, Jani R. Bolla, Carol Robinson
Summary: The use of native mass spectrometry revealed the effects of lipid substrates on PG membrane enzymes and demonstrated that the passage of substrates and products in the pathway is controlled by their relative binding affinities.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Herman K. H. Fung, Shelley Grimes, Alexis Huet, Robert L. Duda, Maria Chechik, Joseph Gault, Carol Robinson, Roger W. Hendrix, Paul J. Jardine, James F. Conway, Christoph G. Baumann, Alfred A. Antson
Summary: Many cellular processes rely on substrate rotation or translocation by a multi-subunit, ring-type NTPase. Researchers have reconstituted a cos packaging system and provided a detailed description of its biochemical and structural properties, revealing similarities and differences in its mechanism and regulation.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Di Wu, Manman Guo, Carol V. Robinson
Summary: Understanding the impact of genetic variations and post-translational modifications on protein interactions is made possible by using native mass spectrometry (MS). In this study, we characterized the proteoforms of plasma serine protease inhibitors and found that different fucosylation linkages have opposing effects on protein interactions.
Article
Biochemistry & Molecular Biology
Daniel A. Bonsor, Dhirendra K. Simanshu
Summary: RAF activation is a crucial step for signal transduction in the MAPK pathway. The SHOC2-MRAS-PP1C (SMP) holoenzyme complex, consisting of SHOC2, MRAS, and PP1C, plays a key role in activating RAF kinases. Recent research has provided valuable insights into the structure and function of the SMP complex, including its assembly, the impact of the nucleotide state of MRAS, and the involvement of SHOC2 and MRAS in PP1C activity and specificity. Understanding the SMP complex could lead to potential therapeutic strategies for RAS/RAF-driven cancers and RASopathies.
Article
Chemistry, Multidisciplinary
Tarick J. El-Baba, Corinne A. Lutomski, Sean A. Burnap, Jani R. Bolla, Lindsay A. Baker, Andrew J. Baldwin, Weston B. Struwe, Carol V. Robinson
Summary: In this study, the impact of glycans on mediating ACE2 dimerization and interactions with Spike was investigated. The researchers found that glycans play a regulatory role in ACE2 dimerization and that positive cooperativity drives ACE2 to complex with multiple Spike trimers. These findings are important for developing strategies to neutralize the virus.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Correction
Biochemistry & Molecular Biology
Rei Matsuoka, Roman Fudim, Sukkyeong Jung, Chenou Zhang, Andre Bazzone, Yurie Chatzikyriakidou, Carol V. Robinson, Norimichi Nomura, So Iwata, Michael Landreh, Laura Orellana, Oliver Beckstein, David Drew
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Review
Pharmacology & Pharmacy
Hsin-Yung Yen, Ali Jazayeri, Carol Robinson
Summary: GPCRs are important drug targets due to their involvement in physiological processes. Mass spectrometry techniques, such as HDX-MS and native-MS, provide opportunities to investigate GPCR pharmacology and discover new drugs. This review highlights the potential of MS techniques for in-depth investigations of GPCR biology.
PHARMACOLOGICAL REVIEWS
(2023)
Article
Multidisciplinary Sciences
Benjamin J. Hardy, Alvaro Martin Hermosilla, Dinesh K. Chinthapalli, Carol V. Robinson, J. L. Ross Anderson, Paul Curnow
Summary: In this study, a minimal diheme membrane cytochrome was computationally designed and produced in live bacteria. The synthetic construct mimics a four-helix bundle found in respiratory complexes and has no sequence homology to natural polypeptides. This artificial membrane metalloprotein has the potential to function as an electron transfer module in both synthetic protocells and living systems.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Gabriela Dias Noske, Yun Song, Rafaela Sachetto Fernandes, Rod Chalk, Haitem Elmassoudi, Lizbe Koekemoer, C. David J. Owen, Tarick V. El-Baba, Carol Robinson, Glaucius Oliva, Andre Schutzer Godoy
Summary: The main protease of SARS-CoV-2, M-pro, is responsible for cleaving the viral polyprotein and is crucial for enzyme dimerization and activity. N-terminal cleavage is not critical for dimerization, and different types of inhibitors can affect the oligomeric states. This study provides insights into the maturation process of M-pro and how it can be targeted by inhibitors.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Changhao He, Jorge Mansilla-Soto, Nandish Khanra, Mohamad Hamieh, Victor Bustos, Alice J. Paquette, Andreina Garcia Angus, Derek M. Shore, William J. Rice, George Khelashvili, Michel Sadelain, Joel R. Meyerson
Summary: CAR T cell therapy utilizes synthetic receptors to guide T cells in targeting and destroying cancer cells. By studying cryo-EM structures and conducting molecular dynamics simulations, researchers were able to create CAR T cells with different tumor recognition sensitivities and understand their requirements for cytolysis and trogocytosis.
SCIENCE IMMUNOLOGY
(2023)
Article
Biochemical Research Methods
Kenneth R. R. Durbin, Matthew T. T. Robey, Lilien N. N. Voong, Ryan T. T. Fellers, Corinne A. A. Lutomski, Tarick J. J. El-Baba, Carol V. V. Robinson, Neil L. L. Kelleher
Summary: Native mass spectrometry has become an important technique for determining the composition of protein complexes. However, there is a lack of software tools for comprehensive analysis of native mass spectrometry data. In this study, we introduce ProSight Native as an informatics platform that can determine the complete composition of protein complexes. We demonstrated its features by successfully determining the composition of a homotetrameric membrane complex and a heterodimer complex with associated ligands.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Multidisciplinary Sciences
Hongmiao Hu, Anne-Marie M. van Roon, George E. Ghanim, Bilal Ahsan, Abraham O. Oluwole, Sew-Yeu Peak-Chew, Carol V. Robinson, Thi Hoang Duong Nguyen
Summary: Shelterin and nucleosomes interact at mammalian telomeres, but the mechanism is not yet understood. Cryo-electron microscopy was used to study the structure of a human telomeric nucleosome bound to the shelterin factor TRF1. The study revealed that TRF1 binds to unwrapped nucleosomal DNA ends by engaging both the DNA and the histone octamer, resulting in a shift in the nucleosomal DNA. Phosphorylation of TRF1 and a noncanonical DNA binding surface on TRF1 were found to be crucial for its association with telomeric nucleosomes. These findings provide important insights into shelterin-chromatin interactions and its roles at telomeres.
Article
Multidisciplinary Sciences
Luke Smithers, Oksana Degtjarik, Dietmar Weichert, Chia-Ying Huang, Coilin Boland, Katherine Bowen, Abraham Oluwole, Corinne Lutomski, Carol V. Robinson, Eoin M. Scanlan, Meitian Wang, Vincent Olieric, Moran Shalev-Benami, Martin Caffrey
Summary: This study investigates the structural changes of the enzyme apolipoprotein N-acyltransferase (Lnt) during its reaction. The study confirms the ping-pong mechanism of Lnt and explains the molecular basis for its ability to bind different substrates.