March 23, 2020
Cow’s milk allergy is the most common allergy that humans have, with 2.5% of the population having it. It usually appears in children less than six months of age. It is important to note that cow’s milk allergy differs from lactose intolerance. This is because lactose intolerance comes from lactase enzyme beta-galactosidase not being able to break-up all the glucose and galactose. Which then is held in the colon and ferments and is why adverse effects occur. Cow’s milk allergy is when an IgE antibody binds to cow’s milk proteins and triggers the release of mediators, such as histamine, prostaglandins, and leukotrienes causing an allergic reaction. The most common cow’s milk proteins are beta-lactoglobulin (BLG pictured), alpha-lactalbumin (ALA), and casein which comprises four proteins coded by different genes carried on the same chromosome: alpas1-caseins, alphas2-caseins, beta-caseins, and kappa-caseins.
March 16, 2020
Crotalus atrox, commonly known as the Texas diamondback rattlesnake, is one of the most dangerous snakes in North America. Untreated bites from C. atrox have a mortality rate of up to 1 in 5, and the species is responsible for a large percentage of the roughly 8,000 venomous snake bites that occur in the US each year. Though its venom is considered to be less toxic than that of most other rattlesnakes, its specialized fangs allow it to deliver much more venom per bite. Like other rattlesnakes, its venom contains several enzymes capable of disabling and destroying other proteins, especially in the bloodstream. Pictured is the enzyme VAP2, a metalloprotease which uses a metallic zinc ion to cleave and disassemble proteins in the target of the bite. The destruction of cellular components by VAP2 is partly responsible for the internal hemorrhaging sometimes caused by rattlesnake bites.
March 9, 2020
We are in the midst of flu season, and while most viruses have no known medications, we have made progress in the cases of Influenza A and B. Oseltamivir - commonly known as Tamiflu - is a medicine that can be taken during the first 48 hours of getting the flu and acts to fight the virus. It works by blocking neuroaminidases on viral surfaces, which in turn stops the release of virions from an infected host cell. Shown here in yellow (PDB ID: 4HZX) is Oseltamavir which slows the spread of the flu if taken early on. It should not be taken as an alternative to vaccinations, so it's still a good idea to go get that flu shot!
March 2, 2020
Could you imagine completely losing the sensation of touch? Imagine your skin meeting a nearby surface yet having no awareness of it. It's probably near impossible to imagine the kind of havoc this would wreak upon our daily lives. If we were to follow the chain reaction that turns the contact of a surface against our skin into conscious awareness of that surface, we would stumble upon a class of proteins called mechanosensitive ion channels (and we would arrive there quite early in the process too). As the name implies, these channel proteins are sensitive to mechanical stimulus - such as changes in tension upon a surface. The specific mechanosensitive ion channel shown is called Piezo2 (PDB ID: 6KG7). It is embeded within the transmembrane, where changes in tension of the membrane opens the channel and allows the influx of ions across the membrane. This activity transforms the mechanical stimulation into electrical activity, which ultimately makes it to the brain - where the surface can be brought to our awareness.
Feb. 24, 2020
Mechanosensitive channels are a type of protein that allow us to hear, maintain balance, and feel touch. They can be found on the membrane (outer "shell") of cells and have evolved to respond to mechanical stress, such as swelling, shrinkage, or deformation of the cell. Mechanosensitive channels can change their shape when the cell is under stress and begin their function in order to prevent osmotic lysis or, in other words, stop the cell from bursting. Shown here is a mechanosensitive channel of small conductance (PDB: 6RLD) which releases solutes and water when a hypo-osmotic shock raises the pressure in the cell.
Feb. 17, 2020
Abrus precatorius, better known as Rosary Pea or Jequirity Bean Plant, produces bright red, hard-shelled seeds. Ingestion of these seeds can be deadly due to the presence of abrin, a highly poisonous protein. Abrin is extremely toxic because it kills cells by inhibiting protein synthesis. The estimated human fatal dose is only 0.1-1ug/Kg and there is no antidote. Abrin (PDBID: 1ABR) consists of two chains (A and B) linked by a disulfide bond. Chain B binds to cell surface receptors, allowing abrin polypeptide to be transported inside the cell via receptor-mediated endocytosis. Inside the cell, chain A uses its glycosidase activity to modify the eukaryotic ribosomes, preventing its binding to elongation factor 2. This inhibits further protein modification during protein synthesis leading to cell death.
Feb. 10, 2020
With the ongoing outbreak of 2019 novel coronavirus, many are quick to remember the spread of Sudden Accute Respiratory Syndrome (SARS) coronavirus that was identified back in 2003. SARS is a more lethal but less infectous type of coronavirus that also started in China, with cross-species infection to humans starting in animal markets. The SARS virus was quickly controlled largely due to public awareness and containment efforts, but perhaps most unprecedented was the amount of collaboration between scientists and researchers around the world at the time, which enabled the identification of the causal agent and genetic sequencing to be accomplished within weeks of the outbreak. Shown here is SARS coronavirus replicative protein NSP9 (PDB ID: 1QZ8), which plays a role in SARS coronavirus replication.
Feb. 3, 2020
You've probably heard a lot about coronavirus lately with the latest infection in Wuhan, China. Coronaviruses are a group of viruses that cause upper respiratory infection in mammals (including humans) and birds. These viruses are envelope viruses with a single-stranded RNA genome. All of us in the scientific community are racing to find a rapid response in the form of a vaccine or treatment. Researchers have identified viral protease M as a potential target for treatment to stop the spread of the virus. Retroviral proteases are enzymes that are vital to the spread of retroviruses such as leukemia viruses and HIV. Not all viruses encode a protease, but those that do ensure that proteolytic action occurs at the proper time and place, independent of a host. In general, these viruses have polyproteins that are cleaved by the viral protease(s) during replication and assembly. Proteases are also involved in mediating virus assembly/disassembly by converting uncleaved, assembled polyproteins into mature capsids capable of disassembling upon virus entry into a newly infected cell. All of these events serve to optimize infection by the virus. Shown in this post is a homology model of the 2019-nCov coronavirus protease created by Innophore [https://innophore.com/2019-ncov/]
Jan. 27, 2020
Collagen is a molecule we’ve discussed before (https://www.instagram.com/p/Bs6Vl-ihArM/). As mentioned, there are 29 versions of collagen – each with unique functions. This week’s #motw is the Pro-Pro-Gly 10:3 triple helix collagen molecule (PDB ID: 1K6F). Many collagen molecules exhibit a PPG motif with various other residues dispersed throughout the sequence. It’s due to this motif that collagen molecules form triple helical tertiary structures and stick to other collagen molecules like “glue”. In fact, the word collagen comes from the Greek word “kólla” which means glue. Fun fact: as we age collagen production and quality reduces in our bodies, but good nutrition helps maintain levels and improves quality.
Jan. 20, 2020
Many proteins targeted by therapeutics are surface proteins. They present on the phospholipid bilayer of cells. These proteins weave in and out of the cell across this layer. The portions of the protein exposed to the bilayer are very hydrophobic and make excellent binding sites! Therefore, when testing whether your therapeutic binds in an ELISA [http://ow.ly/c2Ga50xKJRl] test, you may have false positives because the therapeutic attaches to these hydrophobic portions. Enter the nanodisc (PDB ID: 6CCH). These are mock phospholipid bilayers! The lipids are trapped in between two membrane scaffolding proteins you see here in blue. Surface proteins will naturally stabilize in the bilayer and present just as they would on the cells surface! These nanodiscs have the advantage of assisting solubilization of target proteins and mock the native environment of liposomes.