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Biochemistry

Biochemistry

Study of chemical processes in living organisms

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NYU Grossman School of Medicine
June 10, 2021
www.prnewswire.com:443
/PRNewswire/ -- The signaling molecule hydrogen sulfide (H2S) plays a critical role in antibiotic tolerance, the innate ability of bacteria to survive normally...
June 7, 2021
News-Medical.net
Although extensive studies have been carried out on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and evidence exists that pregnant women are at elevated risk of severe COVID-19, the impact of maternal infection on the fetus is not clear. The majority of pregnant women infected with SARS-CoV-2 are asymptomatic or experience mild symptoms.
Science X staff
April 12, 2021
phys.org
What exactly happens when the corona virus SARS-CoV-2 infects a cell? In an article published in Nature, a team from the Technical University of Munich (TUM) and the Max Planck Institute of Biochemistry paints a comprehensive picture of the viral infection process. For the first time, the interaction between the coronavirus and a cell is documented at five distinct proteomics levels during viral infection. This knowledge will help to gain a better understanding of the virus and find potential starting points for therapies.
Liu, C., Shen, L., Xiao, Y., Vyshedsky, D., Peng, C., Sun, X., Liu, Z., Cheng, L., Zhang, H., Han, Z., Chai, J., Wu, H.-M., Cheung, A. Y., Li, C.
April 9, 2021
Science
When a pollen grain lands on a receptive flower's pistil, a complex dance leading to sexual reproduction begins. Liu et al. show some of the early steps that help to distinguish a compatible pollen grain from a random piece of dust. Normally, a stigmatic gatekeeper, the ANJEA-FERONIA receptor kinase complex, perceives signaling peptides produced by the stigma that drive the production of reactive oxygen species at the stigma papillae. Upon pollination, POLLEN COAT PROTEIN B-class peptides compete with those stigmatic peptides for binding to the stigmatic receptor kinase complex. The subsequent decline of stigmatic reactive oxygen species production allows hydration and opens the gates to pollen germination. Science , this issue p. [171][1] Sexual reproduction in angiosperms relies on precise communications between the pollen and pistil. The molecular mechanisms underlying these communications remain elusive. We established that in Arabidopsis , a stigmatic gatekeeper, the ANJEA-FERONIA (ANJ-FER) receptor kinase complex, perceives the RAPID ALKALINIZATION FACTOR peptides RALF23 and RALF33 to induce reactive oxygen species (ROS) production in the stigma papillae, whereas pollination reduces stigmatic ROS, allowing pollen hydration. Upon pollination, the POLLEN COAT PROTEIN B-class peptides (PCP-Bs) compete with RALF23/33 for binding to the ANJ-FER complex, leading to a decline of stigmatic ROS that facilitates pollen hydration. Our results elucidate a molecular gating mechanism in which distinct peptide classes from pollen compete with stigma peptides for interaction with a stigmatic receptor kinase complex, allowing the pollen to hydrate and germinate. [1]: /lookup/doi/10.1126/science.abc6107
Divine, R., Dang, H. V., Ueda, G., Fallas, J. A., Vulovic, I., Sheffler, W., Saini, S., Zhao, Y. T., Raj, I. X., Morawski, P. A., Jennewein, M. F., Homad, L. J., Wan, Y.-H., Tooley, M. R., Seeger, F., Etemadi, A., Fahning, M. L., Lazarovits, J., Roederer, A., Walls, A. C., Stewart, L., Mazloomi, M., King, N. P., Campbell, D. J., McGuire, A. T., Stamatatos, L., Ruohola-Baker, H., Mathieu, J., Veesler, D., Baker, D.
April 2, 2021
Science
Antibodies are broadly used in therapies and as research tools because they can be generated against a wide range of targets. Efficacy can often be increased by clustering antibodies in multivalent assemblies. Divine et al. designed antibody nanocages from two components: One is an antibody-binding homo-oligomic protein and the other is the antibody itself. Computationally designed proteins drive the assembly of antibody nanocages in a range of architectures, allowing control of the symmetry and the antibody valency. The multivalent display enhances antibody-dependent signaling, and nanocages displaying antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein effectively neutralize pseudovirus. Science , this issue p. [eabd9994][1] ### INTRODUCTION Antibodies that bind tightly to targets of interest play central roles in biological research and medicine. Clusters of antibodies, typically generated by fusing antibodies to polymers or genetically linking antibody fragments together, can enhance signaling. Currently lacking are approaches for making antibody assemblies with a range of precisely specified architectures and valencies. ### RATIONALE We set out to computationally design proteins that assemble antibodies into precise architectures with different valencies and symmetries. We developed an approach to designing proteins that position antibodies or Fc-fusions on the twofold symmetry axes of regular dihedral and polyhedral architectures. We hypothesized that such designs could robustly drive arbitrary antibodies into homogeneous and structurally well-defined nanocages and that such assemblies could have pronounced effects on cell signaling. ### RESULTS Antibody cage (AbC)-forming designs were created by rigidly fusing antibody constant domain-binding modules to cyclic oligomers through helical spacer domains such that the symmetry axes of the dimeric antibody and cyclic oligomer are at orientations that generate different dihedral or polyhedral (e.g., tetrahedral, octahedral, or icosahedral) architectures. The junction regions between the connected building blocks were optimized to fold to the designed structures. Synthetic genes encoding the designs were expressed in bacterial cultures; of 48 structurally characterized designs, eight assemblies matched the design models. Successful designs encompass D2 dihedral (three designs), T32 tetrahedral (two designs), O42 octahedral (one design), and I52 icosahedral (two designs) architectures; these contain 2, 6, 12, or 30 antibodies, respectively. We investigated the effects of AbCs on cell signaling. AbCs formed with a death receptor-targeting antibody induced apoptosis of tumor cell lines that were unaffected by the soluble antibody or the native ligand. Angiopoietin pathway signaling, CD40 signaling, and T cell proliferation were all enhanced by assembling Fc-fusions or antibodies in AbCs. AbC formation also enhanced in vitro viral neutralization of a severe acute respiratory syndrome coronavirus 2 pseudovirus. ### CONCLUSION We have designed multiple antibody cage-forming proteins that precisely cluster any protein A-binding antibody into nanocages with controlled valency and geometry. AbCs can be formed with 2, 6, 12, or 30 antibodies simply by mixing the antibody with the corresponding designed protein, without the need for any covalent modification of the antibody. Incorporating receptor binding or virus-neutralizing antibodies into AbCs enhanced their biological activity across a range of cell systems. We expect that our rapid and robust approach for assembling antibodies into homogeneous and ordered nanocages without the need for covalent modification will have broad utility in research and medicine. ![Figure][2] Designed proteins assemble antibodies into large symmetric architectures. Designed antibody-clustering proteins (light gray) assemble antibodies (purple) into diverse nanocage architectures (top). Antibody nanocages enhance cell signaling compared with free antibodies (bottom). IMAGE: IAN HAYDON, INSTITUTE FOR PROTEIN DESIGN Multivalent display of receptor-engaging antibodies or ligands can enhance their activity. Instead of achieving multivalency by attachment to preexisting scaffolds, here we unite form and function by the computational design of nanocages in which one structural component is an antibody or Fc-ligand fusion and the second is a designed antibody-binding homo-oligomer that drives nanocage assembly. Structures of eight nanocages determined by electron microscopy spanning dihedral, tetrahedral, octahedral, and icosahedral architectures with 2, 6, 12, and 30 antibodies per nanocage, respectively, closely match the corresponding computational models. Antibody nanocages targeting cell surface receptors enhance signaling compared with free antibodies or Fc-fusions in death receptor 5 (DR5)-mediated apoptosis, angiopoietin-1 receptor (Tie2)-mediated angiogenesis, CD40 activation, and T cell proliferation. Nanocage assembly also increases severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus neutralization by α-SARS-CoV-2 monoclonal antibodies and Fc-angiotensin-converting enzyme 2 (ACE2) fusion proteins. [1]: /lookup/doi/10.1126/science.abd9994 [2]: pending:yes
Science X staff
December 15, 2020
phys.org
Scientists from the University of Granada and GENYO have discovered a mechanism via which our cells protect themselves against these transposable or mobile genetic elements, known as "LINE-1," which are involved in the development and progression of many types of cancer
BioSpace
December 3, 2020
BioSpace
Legend Biotech Corporation (NASDAQ: LEGN) ("Legend Biotech"), a global clinical-stage biopharmaceutical company engaged in the discovery and development of novel cell therapies for oncology and other indications, announced today that it has appointed Dr. Patrick Casey as an independent director to Legend Biotech's Board of Directors.
Science X staff
November 30, 2020
phys.org
A research group from the Department of Biochemistry and Molecular Biology of the University of Valencia (UV), in coordination with the National Center for Biotechnology (CNB) of the CSIC, has studied the role of the interactions within the membrane of proteins of viral families Herpesviridae and Poxviridae in the control of programmed cell death. The work, published in Nature Communications, could have implications for the development of treatments for viral infection, as well as the prevention of cancers associated with them.
Mark Terry
May 22, 2020
BioSpace
Every week there are numerous scientific studies published. Here's a look at some of the more interesting ones.
April 30, 2020
clinicaltrials.gov
Treating COVID-19 With Hydroxychloroquine (TEACH) - Full Text View.
Special Correspondent
October 24, 2019
The Hindu
S. P. Subramanian, professor, Department of Biochemistry, University of Madras and V. Krishnakumar, professor, Physics Department, Periyar University, have been chosen.
December 18, 2018
WebWire
A one-day symposium in honor of the late Thomas A. Steitz, PhD, Sterling Professor of Molecular Biophysics and Biochemistry, and Nobel Laureate, will take place on January 18, 2019, from 11 a.m. to 5 p.m. in the Yale Law School auditorium, 127 Wall Street, New Haven. The title of the program is Tom Steitz and the Structural Biology of the Central Dogma. The program will feature the following world-renowned speakers: , , , , , , • Richard Henderson (MRC Laboratory of Molecular Biology,...
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