Want muscles? Rice is the new meat

Darin Goka personifies everything about modern fitness. He does CrossFit. In fact, he loves CrossFit so much, he competes in a league. He's up to date on diet trends. Paleo was nice for a while, but he's kicked it up a notch to vegan. "No animals were harmed in my training," he boasts. So how does this muscle-bound, fat-free specimen of modern manhood get enough protein? Rice. "I feel better," Goka said one afternoon while lifting barbells, jumping rope, and reaching for rings at Valley CrossFit in Los Angeles. The US people have been on a protein-adding craze, throwing powder into smoothies, sprinkling it on foods. General Mills even added protein to Cheerios. One report suggests the whey protein market could hit $12 billion globally by 2017. Soy protein adds a few billion more. However, not everyone wants to get their protein from animals, and some have problems with soy. Leeching protein from sources like wheat or peanuts doesn't help those who can't tolerate gluten or have nut allergies. That leaves rice.   Darin Goka "A long time ago, I realized there was a need for a plant-based protein," said David Janow, CEO of Axiom Foods, the largest producer of plant based proteins in the country. He chose to focus on rice because he thought it would be a great source for boosting protein in animal feed. However, in 2005, "I realized there was a need in human nutrition." Axiom now produces Oryzatein Brown RiceProtein Powder, which it sells under its own Growing Naturals line. It's also sold in products made by manufacturers like Garden of Life and NutriBiotic. Janow estimates 2014 sales of $100 million will double this year. One big reason is that the market is moving beyond just customers with nutritional concerns to fitness enthusiasts. A study published in the Nutrition Journal found that exercise subjects who worked out using whey protein and rice protein had the same performance and recovery. "I feel that it's easier on my stomach," said Goka. Most people think of rice as a carbohydrate, but about eight percent of each grain is made up of protein. Axiom uses a fermentation method to extract and concentrate the protein, and the rest of the grain is used for things like rice syrup. The husks are burned to create power. "Every part of the grain of rice is used," Janow said. Products containing Axiom's Oryzatein are sold in Whole Foods, Sprouts, and small health stores like The Vitamin Barn in Malibu, where it appears in powders sold by NutriBiotic. "In the last five-plus years we've really seen the rice protein just take off in sales as more people become aware of how great the product is," said Kenny Ridgeway, NutriBiotic's director of Purchasing and Manufacturing. "The organic sales since 2011 have increased 204 percent, and actually last year the sales increased 72 percent." Read More : McDonald's to workers: Don't suggest the salad Axiom also sells hemp and pea protein, but rice has the greatest promise. "Rice is very high in leucine, which builds muscle," Janow said. As for cost, Janow claims rice protein is less expensive to manufacture than whey powder. "When they actually polish rice, and they take care of the rice to make it really nice and pristine in the bags, what you see is some of the broken parts. We take a lot of the broken parts, and that's where the value comes in." CNBC.com

Unravelling the complexity of proteins

 

December 1, 2014 International Union of Crystallography Knowledge of the three-dimensional structures of proteins is essential for understanding biological processes. Structures help to explain molecular and biochemical functions, visualize details of macromolecular interactions, facilitate understanding of underlying biochemical mechanisms and define biological concepts. A new article seeks to address the fundamental question of whether the three-dimensional structures of all proteins and all functional annotations can be determined using X-ray crystallography. Knowledge of the three-dimensional structures of proteins is essential for understanding biological processes. Structures help to explain molecular and biochemical functions, visualize details of macromolecular interactions, facilitate understanding of underlying biochemical mechanisms and define biological concepts. The human genome and follow-up sequencing projects have revolutionized biology and medicine; structural genomic programmes have developed and applied structure-determination pipelines to a wide range of protein targets, facilitating the visualization of macromolecular interactions and the understanding of their molecular and biochemical functions. A paper recently published by Mizianty et al. seeks to address the fundamental question of whether the three-dimensional structures of all proteins and all functional annotations can be determined using X-ray crystallography. The researchers set out to perform the first large scale analysis of its kind covering all known complete proteomes (the sets of proteins thought to be expressed by an organism whose genome has been completely sequenced, as defined by the UniProt Consortium in 2012) and all functional and localization annotations available in the Gene Ontology for the corresponding proteins. The Canadian and US team show that current X-ray crystallographic knowhow combined with homology modeling can provide structures for 25% of modelling families (protein clusters for which structural models can be obtained through homology modelling), with at least one structural model produced for each Gene Ontology functional annotation. The coverage varies between super-kingdoms, with 19% for eukaryotes, 35% for bacteria and 49% for archaea, and with those of viruses following the coverage values of their hosts. It is shown that the crystallization propensities of proteomes from the taxonomic super kingdoms are distinct. The use of knowledge-based target selection is shown to substantially increase the ability to produce X-ray structures. Talking to the IUCr Mizianty commented "We believe our method has helped to advance our understanding of the coverage by X-ray structures of proteins and complete proteomes on a global scale." Story Source: The above story is based on materials provided by International Union of Crystallography. Note: Materials may be edited for content and length. Journal Reference: Marcin J. Mizianty, Xiao Fan, Jing Yan, Eric Chalmers, Christopher Woloschuk, Andrzej Joachimiak, Lukasz Kurgan. Covering complete proteomes with X-ray structures: a current snapshot. Acta Crystallographica Section D Biological Crystallography, 2014; 70 (11): 2781 DOI: 10.1107/S1399004714019427

Designer 'barrel' proteins created

 

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The orthogonal views of 5-, 6- and 7-helix barrel proteins created by Drew Thomson, Dek Woolfson and colleagues at the University of Bristol, UK, and described this week in Science. The images show the central channels in these structures to which the team aim to add functions in future.

Proteins are long linear molecules that fold up to form well-defined 3D shapes. These 3D molecular architectures are essential for biological functions such as the elasticity of skin, the digestion of food, and the transport of oxygen in blood.

Despite the wide variety of tasks that natural proteins perform, they appear to use only a limited number of structural types, perhaps just a few thousand or so. These are used over and over again, being altered and embellished through evolution to generate many different functions. This raises the question: are more protein structures possible than those used and presented to us by nature?

A team from Bristol's School of Chemistry and School of Biochemistry, headed by Professor Dek Woolfson, have addressed this by designing humanmade protein molecules from scratch.

Although the design principles used are learned from natural proteins, from which the team develops rules for assembling their proteins, some of the designed protein shapes are completely new and have not been observed in nature yet.

Specifically, the scientists have made proteins with central cavities, or channels, running through them. The team believes that these will be useful in designing new protein functions, such as catalysts for breaking down fats, or molecules that span cell membranes to allow new communications between cells.

Professor Woolfson said: "This is a really exciting time to be exploring what can be done with biological principles and building blocks to make new and useful molecules, but completely outside the context of biology itself. It is one aspect of the emerging field of synthetic biology, in which Bristol is taking a lead both nationally and internationally."

This work has been highly collaborative combining computational modelling, peptide chemistry, biophysics and protein X-ray crystallography across the Schools of Chemistry (Drew Thomson, Antony Burton, Gail Bartlett and Dek Woolfson) and Biochemistry (Richard Sessions and Leo Brady), and an South West Doctoral Training Partnership student (Chris Wood) working between the two Schools.

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Story Source:

The above story is based on materials provided by University of Bristol. Note: Materials may be edited for content and length.

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Journal Reference:

1. Andrew R. Thomson, Christopher W. Wood, Antony J. Burton, Gail J. Bartlett, Richard B. Sessions, R. Leo Brady, and Derek N. Woolfson. Computational design of water-soluble α-helical barrels. Science, October 2014 DOI: 10.1126/science.1257452

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Cellular defense against fatal associations between proteins and DNA

 

Formaldehyde (COH2), generated in cells or derived from the environment, can crosslink DNA to proteins, which interferes with DNA replication. The newly identified repair protein Wss1 chops down the protein component of DNA-protein crosslinks, thereby enabling cells to complete replication.

DNA -- the carrier of genetic information -- is constantly threatened by damage originating from exogenous and endogenous sources. Very special DNA lesions are DNA-protein crosslinks -- proteins covalently linked to DNA. So far hardly anything was known about repair mechanisms specifically targeting DNA-protein crosslinks. Stefan Jentsch's team at the Max Planck Institute of Biochemistry in Martinsried, Germany, now discovered a protease that is able to chop down the protein component of DNA-protein crosslinks, thereby enabling organisms to copy their genetic information even if crosslinks arise.

 The results of this study have major implications for the understanding of genome integrity and cancer development.

The DNA in each cell is highly vulnerable to various types of damage.

A special class of damage is caused by reactive compounds, such as formaldehyde, which are produced as byproducts of cellular reactions and cause the crosslinking (a formation of a covalent linkage) of proteins to DNA. Importantly, these so-called DNA-protein crosslinks are also caused by several anti-cancer drugs and are extremely toxic as they interfere with essential processes such as DNA replication.

Cells need to unwind and separate the DNA double helix in order to copy its genetic information prior to the next round of cell division. DPCs inhibit this process by blocking the way of the unwinding enzyme replicative helicase, thus preventing replication and consequently cell division.

In the laboratory of Stefan Jentsch at the Max-Planck-Institute of Biochemistry, scientists now identified the protease Wss1 as a new safeguarding factor that chops down the protein components of DNA-protein crosslinks and thereby enables cells to duplicate their genome. Julian Stingele, a PhD student in the laboratory, found that cells lacking Wss1 are particularly sensitive to formaldehyde, extremely vulnerable to DNA-protein crosslinks and suffer from genomic instability. Notably, Wss1 has the unique property to cleave proteins only in the presence of DNA, suggesting that the enzyme is well tailored for its task to remove crosslinks from the genome and thus preserve genome stability.

Because the repair of DNA lesions is essential to prevent cancer formation, it is of crucial importance to understand the underlying cellular mechanisms. The newly identified DNA-protein crosslink-repair pathway is particularly important for rapidly dividing cells. Given the fact that cancer cells divide much faster than the majority of human cells, Wss1 might be an attractive future drug target for cancer therapy.

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Story Source:

The above story is based on materials provided by Max-Planck-Gesellschaft. Note: Materials may be edited for content and length.

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Journal Reference:

1. Julian Stingele, Michael S. Schwarz, Nicolas Bloemeke, Peter G. Wolf, Stefan Jentsch. A DNA-Dependent Protease Involved in DNA-Protein Crosslink Repair. Cell, 2014; DOI: 10.1016/j.cell.2014.04.053

Misguided DNA-repair proteins caught in the act

 

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Accumulation of DNA damage can cause aggressive forms of cancer and accelerated aging, so the body's DNA repair mechanisms are normally key to good health. However, in some diseases the DNA repair machinery can become harmful. Scientists led by a group of researchers at The Scripps Research Institute (TSRI) in La Jolla, CA, have discovered some of the key proteins involved in one type of DNA repair gone awry.

The focus of the new study, published in the May 22, 2014 edition of the journal Cell Reports, is a protein called Ring1b. The TSRI researchers found that Ring1b promotes fusion between telomeres -- repetitive sequences of DNA that act as bumpers on the ends of chromosomes and protect important genetic information. The scientists also showed inhibiting this protein can significantly reduce the burden on cells affected by such telomere dysfunction.

"We are very far from therapy, but I think a lot of the factors we've identified could play key roles in processing dysfunctional telomeres, a key event in tumorigenesis [cancer initiation]," said Eros Lazzerini Denchi, assistant professor at TSRI who led the study.

The Trouble with Telomeres

Humans are born with long telomeres, but these become shorter every time a cell in the body divides. With age, telomeres become very short, especially in tissues that have high proliferation rate.

That's when the problems start. When telomeres become too short, they lose their telomere protective cap and become recognized by the DNA repair machinery proteins. This can lead to the fusion of chromosomes "end-to-end" into a string-like formation.

Joined chromosomes represent an abnormal genomic arrangement that is extremely unstable in dividing cells. Upon cell division, joined chromosomes can rupture, creating new break points that can further re-engage aberrant DNA repair. These cycles of fusion and breakage cause a rampant level of mutations that are fertile ground for cancer.

"You basically scramble the genome, and then you have lots of chances to select very nasty mutations," said Lazzerini Denchi.

Setting a DNA Trap

To understand how to prevent these deleterious fusions, Lazzerini Denchi and his colleagues wanted to identify all the repair factors involved.

The researchers decided to set a trap. Using genetically engineered cells, the researchers were able to remove a telomere binding protein called TRF2. Without TRF2, telomeres are unprotected and DNA repair proteins are recruited to chromosome ends, where they promote chromosome fusions.

The researchers then trapped and isolated all the proteins they found bound to the telomeres. "It was like a fishing expedition, and the bait in our case was the telomeric DNA sequence," said Lazzerini Denchi.

Cristina Bartocci, a postdoctoral fellow in Lazzerini Denchi's lab at the time and first author of the new study, spent more than two years perfecting a technique to identify proteins that flocked to the telomeres. "It was a pretty challenging experiment to perform," she said.

The researchers then separated the proteins from the DNA sequences and sent the proteins to TSRI Professor John Yates's laboratory for mass spectrometry analysis. This analysis revealed 24 known repair proteins and 100 additional proteins whose role in dysfunctional telomeres had not been previously described.

The team then refined their search and took a closer look at the role of the repair factor protein called Ring1b. For the first time, the scientists were able to link Ring1b to the chromosome fusion process. Bartocci said the role of Ring1b in dysfunctional telomere repair was "pretty striking."

"If you don't have Ring1b, the process of fusing the chromosomes is not very efficient," said Lazzerini Denchi.

In addition to Ring1b, the team has found nearly 100 factors that might be related to errors in DNA damage repair. The next step in this research is to further refine the long list of DNA repair factors and study other proteins that could affect human health.

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Story Source:

The above story is based on materials provided by Scripps Research Institute. Note: Materials may be edited for content and length.

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Journal Reference:

1. Cristina Bartocci, Jolene K. Diedrich, Iliana Ouzounov, Julia Li, Andrea Piunti, Diego Pasini, John R. Yates, Eros Lazzerini Denchi. Isolation of Chromatin from Dysfunctional Telomeres Reveals an Important Role for Ring1b in NHEJ-Mediated Chromosome Fusions. Cell Reports, 2014; DOI: 10.1016/j.celrep.2014.04.002