Event Begins: Thursday, November 14, 2024 3:00pm
Location: Medical Science Unit II
Organized By: Department of Molecular, Cellular, and Developmental Biology

Mentor: Kristen Verhey

Scientists have demonstrated a creative new way to kill cancer cells effectively, with few side effects. Gluing two particular proteins together tricks the tumors into destroying themselves.

Continue Reading

Category: Cancer, Illnesses and conditions, Body & Mind

Tags: Cancer, Protein, Drug, Stanford University, Apoptosis, Tumor

Heiner Linke, Chair of the Nobel Committee for Chemistry, said the award honored research that made connections between amino acid sequence and protein structure.

The post Nobel Prize in chemistry awarded to 3 scientists for work on proteins, building blocks of life appeared first on Boston.com.

Elementar Americas is partnering with Protein Production Technology International to host a free panel discussion and webinar on “Accelerating Alternative Protein Innovation in the Lab.” It will air on Tuesday, April 30, 2024, at 11:00am EDT/8:00am PDT.

The protein trend has promised to continue at a steady pace, with interest in, and consumption of, plant proteins increasing at record levels. This is due in large part to the rapid expansion in consumer demand for meat, dairy, and seafood analogs. But alongside the growth in protein as a whole ingredient, the various parts that make up a protein molecule are not being ignored. 

Prepared Foods discusses plant protein ingredients and formulation strategies with Charlie Baggs, president, founder and executive chef at Charlie Baggs Culinary Innovations, Chicago.

Sweet proteins are plant proteins that taste up to 5,000 times sweeter than sugar and can replace 70-90% of sugar in most food and beverage products. 

Porphyromonas gingivalis is a major pathogenic oral bacterium that is responsible for periodontal disease. It is linked to chronic periodontitis, gingivitis and aggressive periodontitis. P. gingivalis exerts its pathogenic effects through mechanisms such as immune evasion and tissue destruction, primarily by secreting various factors, including cysteine proteases such as gingipain K (Kgp), gingipain R (RgpA and RgpB) and PrtH (UniProtKB ID P46071). Virulence proteins comprise multiple domains, including the pro-peptide region, catalytic domain, K domain, R domain and DUF2436 domain. While there is a growing database of knowledge on virulence proteins and domains, there was no prior evidence or information regarding the structure and biological function of the well conserved DUF2436 domain. In this study, the DUF2436 domain of PrtH from P. gingivalis (PgDUF2436) was determined at 2.21 Å resolution, revealing a noncanonical β-jelly-roll sandwich topology with two antiparallel β-sheets and one short α-helix. Although the structure of PgDUF2436 was determined by the molecular-replacement method using an AlphaFold model structure as a template, there were significant differences in the positions of β1 between the AlphaFold model and the experimentally determined PgDUF2436 structure. The Basic Local Alignment Search Tool sequence-similarity search program showed no sequentially similar proteins in the Protein Data Bank. However, DaliLite search results using structure-based alignment revealed that the PgDUF2436 structure has structural similarity Z-scores of 5.9–5.4 with the C-terminal domain of AlgF, the D4 domain of cytolysin, IglE and the extracellular domain structure of PepT2. This study has elucidated the structure of the DUF2436 domain for the first time and a comparative analysis with similar structures has been performed.

Metalloproteins are ubiquitous in all living organisms and take part in a very wide range of biological processes. For this reason, their experimental characterization is crucial to obtain improved knowledge of their structure and biological functions. The three-dimensional structure represents highly relevant information since it provides insight into the interaction between the metal ion(s) and the protein fold. Such interactions determine the chemical reactivity of the bound metal. The available PDB structures can contain errors due to experimental factors such as poor resolution and radiation damage. A lack of use of distance restraints during the refinement and validation process also impacts the structure quality. Here, the aim was to obtain a thorough overview of the distribution of the distances between metal ions and their donor atoms through the statistical analysis of a data set based on more than 115 000 metal-binding sites in proteins. This analysis not only produced reference data that can be used by experimentalists to support the structure-determination process, for example as refinement restraints, but also resulted in an improved insight into how protein coordination occurs for different metals and the nature of their binding interactions. In particular, the features of carboxylate coordination were inspected, which is the only type of interaction that is commonly present for nearly all metals.

Tryptophan is the most prominent amino acid found in proteins, with multiple functional roles. Its side chain is made up of the hydrophobic indole moiety, with two groups that act as donors in hydrogen bonds: the Nɛ—H group, which is a potent donor in canonical hydrogen bonds, and a polarized Cδ1—H group, which is capable of forming weaker, noncanonical hydrogen bonds. Due to adjacent electron-withdrawing moieties, C—H⋯O hydrogen bonds are ubiquitous in macromolecules, albeit contingent on the polarization of the donor C—H group. Consequently, Cα—H groups (adjacent to the carbonyl and amino groups of flanking peptide bonds), as well as the Cɛ1—H and Cδ2—H groups of histidines (adjacent to imidazole N atoms), are known to serve as donors in hydrogen bonds, for example stabilizing parallel and antiparallel β-sheets. However, the nature and the functional role of interactions involving the Cδ1—H group of the indole ring of tryptophan are not well characterized. Here, data mining of high-resolution (r ≤ 1.5 Å) crystal structures from the Protein Data Bank was performed and ubiquitous close contacts between the Cδ1—H groups of tryptophan and a range of electronegative acceptors were identified, specifically main-chain carbonyl O atoms immediately upstream and downstream in the polypeptide chain. The stereochemical analysis shows that most of the interactions bear all of the hallmarks of proper hydrogen bonds. At the same time, their cohesive nature is confirmed by quantum-chemical calculations, which reveal interaction energies of 1.5–3.0 kcal mol−1, depending on the specific stereochemistry.

The discovery of lytic polysaccharide monooxygenases (LPMOs), a family of copper-dependent enzymes that play a major role in polysaccharide degradation, has revealed the importance of oxidoreductases in the biological utilization of biomass. In fungi, a range of redox proteins have been implicated as working in harness with LPMOs to bring about polysaccharide oxidation. In bacteria, less is known about the interplay between redox proteins and LPMOs, or how the interaction between the two contributes to polysaccharide degradation. We therefore set out to characterize two previously unstudied proteins from the shipworm symbiont Teredinibacter turnerae that were initially identified by the presence of carbohydrate binding domains appended to uncharacterized domains with probable redox functions. Here, X-ray crystal structures of several domains from these proteins are presented together with initial efforts to characterize their functions. The analysis suggests that the target proteins are unlikely to function as LPMO electron donors, raising new questions as to the potential redox functions that these large extracellular multi-haem-containing c-type cytochromes may perform in these bacteria.

Stimulated by informal conversations at the XVII International Small Angle Scattering (SAS) conference (Traverse City, 2017), an international team of experts undertook a round-robin exercise to produce a large dataset from proteins under standard solution conditions. These data were used to generate consensus SAS profiles for xylose isomerase, urate oxidase, xylanase, lysozyme and ribonuclease A. Here, we apply a new protocol using maximum likelihood with a larger number of the contributed datasets to generate improved consensus profiles. We investigate the fits of these profiles to predicted profiles from atomic coordinates that incorporate different models to account for the contribution to the scattering of water molecules of hydration surrounding proteins in solution. Programs using an implicit, shell-type hydration layer generally optimize fits to experimental data with the aid of two parameters that adjust the volume of the bulk solvent excluded by the protein and the contrast of the hydration layer. For these models, we found the error-weighted residual differences between the model and the experiment generally reflected the subsidiary maxima and minima in the consensus profiles that are determined by the size of the protein plus the hydration layer. By comparison, all-atom solute and solvent molecular dynamics (MD) simulations are without the benefit of adjustable parameters and, nonetheless, they yielded at least equally good fits with residual differences that are less reflective of the structure in the consensus profile. Further, where MD simulations accounted for the precise solvent composition of the experiment, specifically the inclusion of ions, the modelled radius of gyration values were significantly closer to the experiment. The power of adjustable parameters to mask real differences between a model and the structure present in solution is demonstrated by the results for the conformationally dynamic ribonuclease A and calculations with pseudo-experimental data. This study shows that, while methods invoking an implicit hydration layer have the unequivocal advantage of speed, care is needed to understand the influence of the adjustable parameters. All-atom solute and solvent MD simulations are slower but are less susceptible to false positives, and can account for thermal fluctuations in atomic positions, and more accurately represent the water molecules of hydration that contribute to the scattering profile.

Sialic acids play crucial roles in cell surface glycans of both eukaryotic and prokaryotic organisms, mediating various biological processes, including cell–cell interactions, development, immune response, oncogenesis and host–pathogen interactions. This review focuses on the β-anomeric form of N-acetyl­neuraminic acid (Neu5Ac), particularly its binding affinity towards various proteins, as elucidated by solved protein structures. Specifically, we delve into the binding mechanisms of Neu5Ac to proteins involved in sequestering and transporting Neu5Ac in Gram-negative bacteria, with implications for drug design targeting these proteins as antimicrobial agents. Unlike the initial assumptions, structural analyses revealed significant variability in the Neu5Ac binding pockets among proteins, indicating diverse evolutionary origins and binding modes. By comparing these findings with existing structures from other systems, we can effectively highlight the intricate relationship between protein structure and Neu5Ac recognition, emphasizing the need for tailored drug design strategies to inhibit Neu5Ac-binding proteins across bacterial species.

Proteins are well known `shapeshifters' which change conformation to function. In crystallography, multiple conformational states are often present within the crystal and the resulting electron-density map. Yet, explicitly incorporating alternative states into models to disentangle multi-conformer ensembles is challenging. We previously reported the tool FLEXR, which, within a few minutes, automatically separates conformational signal from noise and builds the corresponding, often missing, structural features into a multi-conformer model. To make the method widely accessible for routine multi-conformer building as part of the computational toolkit for macromolecular crystallography, we present a graphical user interface (GUI) for FLEXR, designed as a plugin for Coot 1. The GUI implementation seamlessly connects FLEXR models with the existing suite of validation and modeling tools available in Coot. We envision that FLEXR will aid crystallographers by increasing access to a multi-conformer modeling method that will ultimately lead to a better representation of protein conformational heterogeneity in the Protein Data Bank. In turn, deeper insights into the protein conformational landscape may inform biology or provide new opportunities for ligand design. The code is open source and freely available on GitHub at https://github.com/TheFischerLab/FLEXR-GUI.

Unique protein markers in hair could be used alongside DNA profiling for human identification, according to a study published September 7, 2016 in the open-access journal PLOS ONE by Glendon Parker from Lawrence Livermore National Laboratory, USA, and colleagues.

read more

EPFL scientists have carried out a genomic and evolutionary study of a large and enigmatic family of human proteins, to demonstrate that it is responsible for harnessing the millions of transposable elements in the human genome. The work reveals the largely species-specific gene-regulatory networks that impact all of human biology, in both health and disease.

read more

At the grocery store, most foods -- meats, breads, cheeses, snacks -- come wrapped in plastic packaging. Not only does this create a lot of non-recyclable, non-biodegradable waste, but thin plastic films are not great at preventing spoilage. And some plastics are suspected of leaching potentially harmful compounds into food. To address these issues, scientists are now developing a packaging film made of milk proteins -- and it is even edible.

read more

Exclusive partnership will scale next generation chickpea proteins for North America.

AMCO Proteins has launched HG-80, an all-natural plant-based dough conditioner that reduces mix time.

MGP Ingredients has announced the ProTerra line of textured proteins.

Merit Functional Foods, a solutions-based plant protein company, is pleased to announce that its new 94,000 square-foot facility in Winnipeg, Manitoba, is fully scaled to supply food and beverage customers with the highest purity pea and canola proteins available for use in plant-based applications.

Consumers are seeking out plant-based products for a variety of reasons, but the two most popular factors being that such options are better for their health and better for the planet, experts note.

As beverage-makers increasingly turn to plant proteins to meet consumer trends, experts highlight some key considerations to take into account when formulating with these ingredients.

A study conducted by Harvard-affiliated Brigham and Women’s Hospital revealed that individuals experiencing a broad array of long COVID symptoms are twice as likely to have traces of SARS-CoV-2 proteins in their blood compared to those without symptoms of long COVID. The symptoms frequently associated with long COVID include fatigue, brain fog, muscle and joint pain, back pain, headaches, sleep issues, loss of smell or taste, and gastrointestinal problems.These findings were published in the journal Clinical Microbiology and Infection.

These novel insights will hopefully lead to better treatments for lupus patients, now that we may know why the body attacks itself in this disease.

These novel insights will hopefully lead to better treatments for lupus patients, now that we may know why the body attacks itself in this disease.

These novel insights will hopefully lead to better treatments for lupus patients, now that we may know why the body attacks itself in this disease.

Large scale plasma proteomics identifies novel proteins and protein networks associated with heart failure development  Nature.com

Pick-up single-cell proteomic analysis for quantifying up to 3000 proteins in a Mammalian cell  Nature.com

An interactive atlas of genomic, proteomic, and metabolomic biomarkers promotes the potential of proteins to predict complex diseases  Nature.com

Single-tissue proteomics in Caenorhabditis elegans reveals proteins resident in intestinal lysosome-related organelles  pnas.org

Identifying proteomic risk factors for cancer using prospective and exome analyses of 1463 circulating proteins and risk of 19 cancers in the UK Biobank  Nature.com

The latest step in brand's sustainability journey is expected to reduce more than 90 percent of plastic use across all canister offerings.

Custom designing proteins — a breakthrough recognized by the latest Nobel Prize in chemistry — could yield treatments that stop the worst of COVID-19 before it begins.

The post Stanford Medicine experts help Nobel winner custom design proteins for COVID-19 therapy appeared first on Scope.

Location: Electronic Resource- 

Compartmentalized protein expression in the spider silk gland provides clues to spinning more sustainable materials. 

Numerous iron-sulfur (Fe-S) proteins with diverse functions are present in the matrix and respiratory chain complexes of mitochondria. Although [4Fe-4S] clusters are the most common type of Fe-S cluster in mitochondria, the molecular mechanism of [4Fe-4S] cluster assembly and insertion into target proteins by the mitochondrial iron-sulfur cluster (ISC) maturation system is not well-understood. Here we report a detailed characterization of two late-acting Fe-S cluster-carrier proteins from Arabidopsis thaliana, NFU4 and NFU5. Yeast two-hybrid and bimolecular fluorescence complementation studies demonstrated interaction of both the NFU4 and NFU5 proteins with the ISCA class of Fe-S carrier proteins. Recombinant NFU4 and NFU5 were purified as apo-proteins after expression in Escherichia coli. In vitro Fe-S cluster reconstitution led to the insertion of one [4Fe-4S]2+ cluster per homodimer as determined by UV-visible absorption/CD, resonance Raman and EPR spectroscopy, and analytical studies. Cluster transfer reactions, monitored by UV-visible absorption and CD spectroscopy, showed that a [4Fe-4S]2+ cluster-bound ISCA1a/2 heterodimer is effective in transferring [4Fe-4S]2+ clusters to both NFU4 and NFU5 with negligible back reaction. In addition, [4Fe-4S]2+ cluster-bound ISCA1a/2, NFU4, and NFU5 were all found to be effective [4Fe-4S]2+ cluster donors for maturation of the mitochondrial apo-aconitase 2 as assessed by enzyme activity measurements. The results demonstrate rapid, unidirectional, and quantitative [4Fe-4S]2+ cluster transfer from ISCA1a/2 to NFU4 or NFU5 that further delineates their respective positions in the plant ISC machinery and their contributions to the maturation of client [4Fe-4S] cluster-containing proteins.

Alfred C. O. Vertegaal
Dec 1, 2006; 5:2298-2310
Research

Ileana M. Cristea
Dec 1, 2005; 4:1933-1941
Research

Hasmik Keshishian
Dec 1, 2007; 6:2212-2229
Research

Tamar Geiger
Mar 1, 2012; 11:M111.014050-M111.014050
Special Issue: Prospects in Space and Time

William M. Old
Oct 1, 2005; 4:1487-1502
Research

Leigh Anderson
Apr 1, 2006; 5:573-588
Research

Jeffrey C. Silva
Jan 1, 2006; 5:144-156
Research

Ulrich Rothbauer
Feb 1, 2008; 7:282-289
Research

Eiji Kinoshita
Apr 1, 2006; 5:749-757
Technology

M el-Saadani
Apr 1, 1989; 30:627-630
Articles

M. Burstein
Nov 1, 1970; 11:583-595
Articles

JL Dixon
Feb 1, 1993; 34:167-179
Reviews