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The mitochondria are the powerhouse of the cell, and ATP synthase molecules are the generators that drive them. Adenosine triphosphate, usually abbreviated ATP, is often referred to as the "energy currency" of the cell. It provides the fuel for countless cellular reactions. In order to produce ATP, cells metabolize sugars, and use that energy to push hydrogen ions up an “energy hill,” creating a difference in ion concentration across a membrane. Much like how hydroelectric dams use turbines to capture energy from flowing water and turn it into electricity, ATP synthase captures the energy of the ions flowing back “downhill” using a spinning protein rotor. As this rotor moves inside the “turbine”, it provides the energy necessary to create new ATP to power the cell!

DNA->RNA->Protein. This progression is called the central dogma of biology. In the first step of this process, DNA is transcribed to messenger RNA molecules that then go on to be translated into proteins that do the work of cell processes. As such, there are many ways to regulate transcription. Proteins involved in the regulation of transcription are called transcription factors. These proteins can upregulate or downregulate how much a gene is expressed. Shown here is the transcription factor CDX2 bound to DNA. PDB: 5LTY

Happy New Year from the Macromoltek team! Here is your science fact for the day! Signaling proteins are extremely important for maintaining cells in a healthy state and regulating processes like metabolism and proliferation. In particular, Rab GTPases are master regulators of intracellular trafficking. Since Rab proteins are implicated in multiple aspects of tumour progression including tumour cell migration, invasion, proliferation, communication with stromal cells, and the development of drug resistance. As a consequence, Rab proteins may be novel potential candidates for the development of anticancer drugs.

Although we dont yet understand how to effectively cure Parkinson’s disease, a recent breakthrough will hopefully lead to new insights and therapies for the future. Mutations in the PINK1 gene cause early onset Parkinson’s disease. PINK1 is a kinase that, in healthy cells, is processed in the mitochondria and regulates the differentiation of neurons. Recently, a crystal structure was published of PINK1, hopefully resulting in more information to understand the molecular mechanisms of this debilitating disease.

Much like how skeletons help support the bodies of vertebrates, cells have a network of structures which help keep them their shape too. This network, called the cytoskeleton, consists of a large number of microtubules and microfilaments. In addition to helping the cell stay stable, it assists in cell movement and division, moving cargo around the cell, and countless other processes. The microfilaments in the cytoskeleton consist of a flexible helical polymer of a protein called actin. Because microfilaments are so important to so many cellular functions, actin has changed very little over the course of evolutionary history, which means that actin in humans is about the same as actin in everything from nematodes to algae!

Huntington's disease it thought to be caused by a mutation in the huntingtin protein that results in an extra 36 or more glutamine residues. Huntingtin protein already has a high concentration of glutamine residues, with wild-type containing 6-35 glutamine, whereas the protein in diseased individuals can contain upwards of 250! The function of the protein is unknown, however it is thought to play an important role in nerve cells and is required for normal development after birth. PDBID: 3IOW

Our immune systems include a long list of defenses ready to stop pathogens every step of the way. The very first of these defenses is the outer layer of our skin called the epidermis. The epidermis is made of specialized cells called keratinocytes specifically named because they produce a structural protein called keratin en mass. The life of keratinocytes is really quite interesting! Keratinocytes start their lives as epidermal stem cells and randomly become a short-lived progenitor called a “transit amplifying cell”. This cell type continues to divide and migrate towards the outer layer of the epidermis. Along the way, the cell differentiates a few times and takes on new behaviors and characteristics. The final stage of the keratinocyte is the corneocyte. This cell is characterized by exiting the cell cycle, losing its nucleus and cytoplasmic organelles, and having its plasma membrane replaced with a host of keratin-proteins. This new keratin membrane is enveloped by an insoluble amalgam of proteins and linked by transglutamines and lipids. That’s the skin you see and touch! It’s made of proteins and fats. In fact, keratin forms a whole list of structures including hair, nails, hooves, feathers, horns, etc. which distinguish themselves by amount and type of keratin produced. There are dozens of different types of keratin, but each are structurally quite similar as you can see from the picture which includes keratins 1 and 10. Info about differentiation from: https://www.proteinatlas.org/humanproteome/skin

What makes cells grow? Growth factors are any of a group of proteins that stimulate the growth of specific tissues. They play an important role in promoting cellular differentiation and cell division. They bind to receptors on the cell surface, with the result of activating cellular proliferation and/or differentiation. Growth factors are quite versatile, stimulating cellular division in numerous different cell types; while others are specific to a particular cell-type. The loss of or decreased requirement for specific growth factors is a common occurrence in neoplastically transformed cells and may lead to a growth advantage, a cardinal feature of cancer cells. Recent work with transforming growth factors, the platelet-derived growth factor, and oncogenes has produced some insight into the mechanisms through which alterations in growth factor-receptor-response pathways could lead to a growth advantage. PDB: 4QCI is a blocking Anti-Platelet-Derived Growth Factor (PDGF) monoclonal antibody

Myoglobin is a small protein which stores oxygen for your muscle cells to use when they need it most. It contains a special disk-shaped molecule called heme, which has a perfectly sized hole in its center that lets it hold an oxygen molecule for later use by the cell. Myoglobin is important for muscular function, but it is a special molecule in structural biology for a different reason altogether: myoglobin was the first molecule to ever have its structure determined by x-ray crystallography! John Kendrew won the 1962 Nobel Prize for his structure of myoglobin, and laid the foundations for thousands of structural biologists to follow in his footsteps. By 1982, the Protein Data Bank already contained 100 such structures, and in 2014, it surpassed 100,000! Structural biology has really come a long way in the past sixty years, and it all started with myoglobin.

Penicillin is a broad-spectrum antibacterial drug, but few of us have considered how this drug performs its primary function. Essentially, penicillin reduces the integrity of bacterial cell walls. Bacteria are constantly replenishing their cell walls when growing or reproducing much like we regenerate our skin. Expansion is accomplished via a network of enzymes and peptidoglycans, the cell wall “bricks”. Penicillin-binding proteins (PBP) belong to a subgroup of enzymes called transpeptidases and are the essential “brick-layers” for bacteria. PBPs catalyze the reaction between peptidoglycans by mediating the removal of D-alanine from the precursor of peptidoglycan. This results in a conformational change and binding of adjacent peptidoglycans. Penicillin acts as an inhibitor for this reaction. The structure of penicillin is very similar to that of the peptidoglycans, so PBP forms a bond with penicillin at the active site. In fact, it’s a covalent bond, so it’s irreversible! PBP is thence rendered inactive, peptidoglycans are left unlinked, and the bacterium’s cell wall is full of holes. Osmotic pressure builds on the bacterium as the cell wall further degrades and eventually leads to cell death. Better them than you! PBPs come in a variety. Pictured here is Penicillin-binding Protein 2a from a resistant strain of Staphylococcus Aureus strain 27r. This bacteria evolved a mutation which allows its PBP2a to resist binding to penicillin. PDB: 1VQQ