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Rheumatoid-arthritis (RA) is an autoimmune disease where your body attacks your connective tissues, primarily the joints, heart, and lungs. The way this disease works is much like other autoimmune diseases; the body releases antibodies which bind to native tissues. Once attached, the antibodies signal to your immune cells to ATTACK! This releases histamine and other cell-killing chemicals which cause the connective tissue to become inflamed and damaged. The release of histamine is a positive feedback loop, so more histamine is released to the area. Thus the pain of RA can become progressively worse once symptoms arise. Patients often report having good days and bad days, depending on a variety of factors such as stress, smoking, and level of physical activity. Over time, the damage can cause joints to become stiff and unstable. It is unknown how and why RA starts, but it is linked to genetics. Fortunately, treatment for RA is fairly effective and can dramatically increase quality of life. Pictured is the protein 1ADQ which is a characteristic antibody of RA.

Many of our interactions and observations in our everyday life are made possible due to the complicated system that allows us to hear. One of the unsung heroes of the inner ear is Cadherin-23. Many of us are familiar with the sensitive "hairs" in our cochlea that respond to the vibrations caused by auditory stimulation. These "hairs" are actually stereocillia (upper left) that are long, thin projections from cells that line the inside of the inner ear. As sound waves pass through these stereocilia, they bend, causing the distance between the tips to increase. Cadherin-23 serves to link these tips together, and pulling on it activates a protein called an ion channel. This, in turn, fires up the nerve underneath the hair cell and sends a message to the brain that sound waves are traveling through the ear. Feel free to let us know what you use Cadherin-23 for in a comment below!

Programmed cell death protein 1 (PD-1) is found on the surface of cells and plays a role in regulating against autoimmunity by preventing the immune system from attacking our body's own healthy tissues. Programmed death-ligand 1 is a protein (also found on cell membranes) that binds to PD-1 to send a signal promoting apoptosis (cell death) in antigen-specific T-cells. This mechanism blocks these specific T-cells from reaching their target, such as healthy cells, and therefore prevents autoimmune diseases. Unfortunately, PD-L1 has been found on the surface of cancer cells. The T-cells are unable to attack the cancer, allowing the disease to proliferate. Cancer immunotherapy takes advantage of this type of knowledge to create antibodies that can bind to certain proteins and guide the immune system toward eliminating cancer cells. Shown is an example of this (PDB 5ggs) where Prembrolizumab, an antibody drug approved by the FDA, binds to PD-1 and functionally prevents cancer cells from "hiding" from our immune system. At @macromoltek , we use our in-house antibody modeling and design software to aid in the development of life-changing antibodies just like these.

They say that love heals, but is there any scientific basis to the statement? Neurophysin is a neurohypophysial hormone that functions as a carrier protein to move molecules along axons from the hypothalamus to the posterior lobe of the pituitary. One of the molecules it is known to carry is Oxytocin (OXT) - the love drug! Another molecule this carrier protein transports is arginine vasopressin (AVP), which has been associated with hypertension. When too much AVP is carried, the concentration in the blood increases and contributes to pressure elevation through an unknown mechanism. So back to our original question: can love heal? Science has shown that emotional bonds during periods of extreme duress can increase the amount of OXT that is released. This release is what triggers the feelings of love, but it also has anti-oxidant and anti-inflammatory properties that have been shown to protect against atherosclerosis or, as you may know it, heart disease. Shown here is neurophysin II bound to oxytocin (in red), ready to be transported and provide its healing powers. PDB: 1NPO.

You may have heard the medical advice to avoid grapefruit juice consumption while taking a statin. The action of grapefruit juice on the effect of drugs was discovered by accident in 1989 in an experiment designed to examine the effect of ethanol on the action of felodipine, a calcium channel blocker. Grapefruit juice was used to mask the taste of alcohol, but the results showed several-fold higher felodipine concentration in blood plasma than had been expected. Grapefruit juice has since been shown to interact with over 85 drugs, including statins, which are widely used to reduce low-density lipoprotein (LDL) cholesterol to help prevent cardiovascular disease. Newer studies have determined that the increased rhabdomyolysis risk from grapefruit juice consumption due to the increased effective statin dose is minimal compared with the greater effect in preventing heart disease. Maybe grapefruit juice should not be contraindicated in people taking statins!

Caffeine, found in coffee, tea, chocolate, and a variety of other foods and drinks, is probably the most popular drug in the world. It works by tightly binding to adenosine receptors in the central nervous system. Normally, as adenosine levels in the brain rise throughout the day, these receptors send signals that increase drowsiness - but caffeine blocks adenosine from binding them, preventing you from feeling tired! In addition to keeping you awake and alert, caffeine also improves concentration, boosts motor coordination, and stimulates a release of dopamine. It's no surprise, then, that estimated global caffeine consumption tops 100,000 tons a year! This is the structure of adenosine receptor A2A with caffeine bound (yellow) PDB: 3RFM.

Everyone in bio 101 learns that mitochondria are the powerhouse of the cell. We were taught that it's an organelle and maybe your professor mentioned that they have their own genome. Did you ever stop to think what that really implies, though? One of the oldest ancestors of complex life on Earth was a nucleated cell that either didn't digest a prokaryote it enveloped or couldn't digest it due to some mutation. Fortunately, this resulted in a symbiotic relationship where the prokaryote produced ATP that the nucleated cell utilized. Meanwhile, the prokaryote was able to thrive in the protective environment. These two cells evolved together and the prokaryote became what we know as the mitochondria. Though our eukaryotic cells rely on mitochondria and vice versa, mitochondria remain largely autonomous. Retaining their own genome is the prime example, but another is their ability to divide independent of their hosts. This process is regulated by the host so mitochondria don't multiply enough to cause a rupture! One protein mammalian hosts use to regulate mitochondrial fission is called MFN1 and is presented here (PDB: 5YEW).

Almost 2 years ago we featured the molecule amyloid-beta (Aβ) on our Instagram. This troublesome little protein causes Alzheimer’s disease (AD)! See the post here: http://ow.ly/kAaW30kWJ4x. At the time there were no effective treatments that could cure or dramatically slow down the progression of the disease. A new antibody, Aducanumab, that targets Aβ, is in Phase 3 clinical trials for the treatment of AD. The graph presented here (http://ow.ly/qbD530kWJGz) shows Aducanumab binding to a linear epitope formed by amino acids 3-7 of the Aβ peptide (PDB ID: 6CO3). Aducanumab discriminates between monomers and oligomeric or fibrillar aggregates based on weak monovalent affinity, fast binding kinetics, and strong avidity for epitope-rich aggregates. These biochemical and structural studies provided a strong rationale for treating AD by targeting specific species of the Aβ protein.

Neurotrophins are proteins responsible for the development and maintenance of our nervous system. They belong to a class of growth factors, which regulate cell growth, proliferation, and healing. The Nerve Growth Factor (NGF) was the first neurotrophic factor to be discovered and is involved in signaling processes such as cell differentiation, survival, and apoptosis (cell death) of neurons. NGF can bind to two different cell receptors; TrkA and p75. Shown is NGF and domain 5 of TrkA in complex (PDB ID: 1WWW) and, while NGF-TrkA signaling promotes neuron growth, this function declines after birth and plays a bigger role regulating the sensitivity of the peripheral nervous system to harmful stimuli. Furthermore, NGF concentration has shown to increase in chronic pain conditions, suggesting its involvement in chronic nociceptive states. A promising treatment currently under development is anti-NGF antibodies, which would not only provide a solution but also serve as a better alternative to opioids and anti-inflammatory drugs.

Every October through May we hear all about the influenza virus, commonly known as the flu, and most of us get our flu shots. Why do we need a new flu shot every year? Well, the flu virus is constantly changing! The target epitopes mutate and new vaccines take these mutations into consideration. On top of this, no one knows what the mutation will be, but scientists have a pretty good guess. However, when the guess is wrong, it could have detrimental outcomes (like N1H1 was many years ago). Pictured is a complex with the Influenza A virus and antibodies binding to it. Antibodies are the body’s way of fighting back against infection. The antibodies present in this complex came from a mouse and were the first antibodies identified to cross-neutralize multiple sub-types of influenza A. This means that these antibodies can fight against multiple different strains of the flu, so when it mutates every year they still work. These antibodies could be humanized and used to fight back against lots of different strains of the flu. (PDB: 4HLZ)