Protein Portraits

Hemocyanin

PDB ID: 1NOL

Blue Blood? That a Hemo-SIGN-anin that you have Hemocyanin in your blood! Hemocyanin is a protein that is found in molluscs, such as snails, octopi, and crabs, and it carries oxygen just as hemoglobin does in our bodies. Similar to hemoglobin, a central metal atom binds oxygen, but in hemocyanin, this central atom is copper, which is represented in my model with copper wire and 2 blue ball structures. The blue beads of the various creatures represent the hemocyanin circulating in their blood. They are floating to represent the free floating quality of this protein. Oxygenation causes a color change between the colorless Cu(I) deoxygenated form and the blue Cu(II) oxygenated form, making the blood of the creatures appear blue!

Here are some photos from the development of the Hemagglutinin model

1918 Influenza Hemagglutinin

PDB ID: 1RUZ

Raha Kannan

Hemagglutinin, a trimeric transmembrane protein found on viral membranes, helps viruses enter and release their viral RNA into cells. The outer portion of the protein targets sialic acid chains (present on glycoproteins) on cell membranes to “dock” the virus on the cell surface. Once the virus is internalized via endocytosis, the cell releases acids to digest the endosomal contents. However, the lower pH induces a conformational change in the protein, allowing the internal portions (initially folded and hidden under the outer parts) to attach to the endosomal membrane. The protein then pulls the viral and endosomal membranes together, allowing them to fuse together and to release viral RNA into the cell. I chose to model Hemagglutinin using tissues (folded into carnations) since this particular Hemagglutinin model was from the 1918 influenza virus. The tissue flowers were colored by spraying food coloring onto them; the alpha helices on the inside were represented by curled pipecleaners; and the part of the protein that attaches to the endosomal membrane was represented by paperclips.

Human Ceruloplasmin

PDB ID: 4ENZ

Karissa Renyer

Ceruloplasmin is the main copper-carrying protein in the blood. However, it also is a ‘moonlighting’ protein, performing various other functions outside of its typical role with copper. For example, it also acts as a ferroxidase, catalyzing the oxidation of iron (II) to iron (III). This pendant is made of copper to highlight ceruloplasmin’s role with copper ions. Additionally, this protein is naturally blue, so a blue-green patina was used to alter the color of the piece to reflect this characteristic. The raised pieces of copper (free of the patina finish) represent the six approximate locations that copper binds to the protein.

Couldn’t get a molded plastic form to have enough freedom to move so I went with wood, metal, and plastic. I also modified a mechanical cart to help it walk.

I was able to use a blue patina today on my ceruloplasmin protein pendant. Here is a before and after picture showing the transformation brought forth from the patina! I ended up sanding off the patina on the raised copper portions of the pendant to highlight the copper binding sites present in the actual protein.

Thanks to all who pitched in with some important 10th week committee work:

• Show tables committee.  We have tables!
• Our show ballot committee.  Clever categories!
• Our show poster committee.  Splendid artistic view of a Nobel prize winning ion channel structure discovered by Rod MacKinnon . The artist is Steve Miller. Note the fascinating inclusion of CPK models in the artwork (where P stands for our very own Linus Pauling!)

See you all on Thursday!

This weekend I build the wireframe for my protein project (see left). It looks much better in person than in the picture, but still needs some added volume around the wires to give it more form. I plan to do this with silicone I got from Home Depot. Silicone is the rubber-like material that is typically used as a sealant for tiles. I found that silicone is easy to apply and sculpt, but maintains its shape if left alone.

Right is the structure of one of the chains of GFP (PDB ID: 1gfl). The general shape looks similar to the wire model. Something I noticed, though, is that the model has the opposite orientation for the helix. Oops! I suspect that this detail will not significantly interfere with the intention of the composition. Time permitting, I may correct the orientation in the future.

Today, I am planning on visiting Home Depot again to obtain more silicon and some paints.

Raha is just back from visiting the Art of Brick exhibition at OMSI (in Portland).  Check it out!

The widely used pymol is available here. Highly recommended for adjusting your view as you work on your protein portraits projects.

The Protein: Hemagglutinin (HA), a protein involved in the viral infection process. Specifically, HA helps cells internalize the virus and eventually the viral RNA.

Structure: Hemagglutinin is a trimeric transmembrane protein that extends from the surface of viruses. There are two types of chains in the enzyme, which we can call HA I and HA II. HA I (shown in blue) sits on the top of the protein while HA II (shown in yellow) is partially covered by HA I at first. There are also various carbohydrates on the Hemagglutinin surface. The viral strain (H1,H2, etc) can change if the location of the carbohydrate chains on the HA surface changes.

Hemagglutinin extending from virus surface

You can view the various hemagglutinin structures on PYMOL using the following PDB IDs:

• 1RD8 – uncleaved hemagglutinin from the 1918 influenza virus
• 1RUZ – the active form of hemagglutinin from the 1918 influenza virus

Mechanism of Action: 

Video 1 shows the whole influenza virus infection process

Video 2 (skip to minute 4) shows the membrane fusion process

The blue portion of the protein targets sialic acids, which are part of some glycoproteins found on the cell membrane. Once the virus is docked on the cell membrane surface the cell internalizes the entire virus via endocytosis and begins releasing acids meant to digest the endosomal contents. However, the acids actually help activate conformational changes in Hemagglutinin, which allow the red portion of the protein to attach to the endosomal membrane. The yellow portion of the protein then moves up the the protein and brings the viral and endosomal membranes together. The viral RNA can enter the cell after the two membranes fuse together.

Hemagglutinin conformational changes

Modeling Ideas:

Some combination of these

1.Different colored flowers made of tissue to represent the different parts of the protein joined together by pipe cleaners or wire or something similar since the protein looks like a flower bouquet from certain angles. And tissues are the only cold/flu related material I can think of.

2. Tissue flowers for the HA I portion and then spiral bracelets to represent the alpha helices on the inside. Show conformational changes by moving the different pieces. Use a safety pin/bobby pin structure to pull two “membranes” (pieces of cloth?) together to represent the fusion of the viral and cell membranes.

3. Play-doh model of the three different stages?

Tissue carnations

Spiral bracelet

This was news a few months ago but the Weihong Qiu lab in the Physics/Biophysics lab observed and reported that kinesin can walk backwards. It was previously thought that kinesin could only walk forward, in fact the Hoogenraad Lab video on kinesin even mentioned that it could only walk forward.

Here is the post on the Physics webpage; A biological motor that switches gears from forward to reverse

Also here is a funny animation for myosin on a single strand of actin by Erin Craig (CWU).

Let me introduce Erythrocruorin, giant hemoglobin made from earthworms. This hemoglobin is HUGE, it is comprised of 144 globin chains and its skeleton is comprised of 12 globin chains. Each of these chains can carry oxygen and with its 3-fold symmetry, the real reason I noticed it, it kinda acts like a rock tumbler or a rattler. The oxygen rattle around bonding randomly in its skeleton structure but never being allowed to escape. Maybe this is more like one of those cat/dog toys containing a treat. Tell me what you think!

TMV is the first virus to be discovered and is found to be mostly made of protein. It is supposed to be very stable and can survive for years within a cigar or cigarette.

TMV’s helical shape kind of reminds me of tubulin and how it forms dimers to make microtubules. Though they do not form in quite the same way, they both have the ability to rapidly assemble and disassemble which reminded me of this origami paper tower below. It’s a dynamic structure that can be squished or stretched out (a decent representation of the rapid assembly/disassembly).

Actinomycin, discovered in Streptomyces antibioticus in 1940, is the first natural antibiotic that has anti-cancer activity. Unfortunately, actinomycin does not specifically kill cancer cells, so it too toxic for general use. This molecule works by intercalating into the DNA double helix and interfering with topoisomerase activity. Topoisomerases, which untangle and reduce tension of DNA strands in cells, break down DNA before making topological changes and reassembling the DNA. Actinomycin and other intercalating drugs prevent topoisomerases from reassembling the DNA after it has been broken down. Actinomycin (shown as the green/blue structure in the figure below) is composed of two parts:

1. a flat ring (shown in green) that resembles DNA bases, and
2. two cyclic peptides composed of unusual amino acids (shown in blue)

Actinomycin intercalates between the bases in a DNA helix

To represent actinomycin artistically, we can use a half unraveled bracelet  to represent DNA with a knot or bead to represent actinomycin and the effect it has on DNA. We could also used a half tangled slinky to represent DNA with something jammed in between the layers to represent actinomycin.

Proteasomes break down other proteins. They help keep the cell free of damaged proteins as well as allowing the cell to  recycle parts of proteins that it no longer uses. In this image, the yellow and red core is where the proteins are broken down. The blue ends recognize ubiquitin tagged proteins and starts pulling them in, while the pink part unfolds them and passes them in to the core.

This protein reminded me of a pencil sharpener, especially the twisted core in the middle. The core reminded me of the center of a classroom pencil sharpener, and the outer parts of the protein are kind of similar to the holes in a pencil sharpener that only let the right size of pencil through. If you attached two pencil sharpeners back to back and put on a casing that looked more like the protein shape, you could have a fairly accurate representation of a proteasome that would also be able to sharpen two pencils at the same time.

This is the P-Glycoprotein found in many cells of the human body. It’s role is to search for toxic molecules and eject them from the cell to be disposed. Using ATP, the P-Glycoprotein targets mostly hydrophobic toxic molecules in its deep opening and then changes shape to allow the molecule to escape outside of the membrane. The protein can target hundreds of toxic molecules from as small as 10 atoms to as large as hundreds of atoms.

In order to artistically portray this protein, one could have two small seesaw shapes with the seats facing each other. The seesaws would shift at the same time to connect on the other side.

Sodium-potassium pumps create and maintain electrochemical gradients, pumping potassium ions into the cell and sodium ions out of the cell. The established gradient is a crucial part of sending electrical nerve signals and regulating the osmotic pressure in cells. When the axon of a nerve cell experiences a depolarization in membrane potential, sodium-potassium pumps are responsible for reestablishing the resting potential of the membrane. This allows the axons of nerve cells to be prepared to transmit the next signal.

Since sodium-potassium pumps are partially responsible for the transmission of electrical nerve impulses, one way to represent the protein would be in such a way to resemble a lightning bolt. It might be unique to sculpt the protein with wire and small LED lights in the shape of lightning to represent one of its key functions.

Aquaporin creates a channel for water molecules to pass through a membrane, so this molecules pops up when talking about osmosis. Aquaporin can be found in many organisms, from bacteria to eukaryotes and is made up of 4 identical chains.  The molecule itself is somewhat stationary with some rotation in the membrane, but the water molecules allow us to visualize how the function of the aquaporin is important.

When visualizing this molecule, there are a few different approaches that can be made. From the video above, you can see the bounciness of the water molecules as they pass through the aquaporin molecule. This reminds me of an arcade or carnival game that has the floating balls and you have to knock the balls down with a bigger ball or a sack. When the bigger ball misses and passes through the floating balls, there is a bounciness that can occur due to the gust of wind or movement. The aquaporin molecule in this case would be the machine that blows the balls up in the air and allows it to bounce.

Similarly, this model reminds me of a kinetics ball that can expand and allow things to pass through it (such as a bouncy ball) or a filter or colander that strains and separates.

This week please post a protein example from the Molecule of the Month and include an idea of how the dynamics of that protein could be conveyed artistically!

Here’s a quick rundown of the artwork we looked at on Tuesday when we were discussing the portrayal of action:

• Velazquez’s Portrait of Prince Balthasar
• Gainsborough’s Blue Boy
• Degas’s Dancer on Stage
• Duchamp’s Nude Descending a Staircase
• Edward Muybridge’s photographs of moving animals (and people)
• The zoetrope: A device for viewing successive frames in a sequence of images

Hang on!

Hi all,

I wanted to say thanks for a great semester, and wanted to share this cool game I found! Foldit is a protein folding game was developed by the University of Washington. As more people play the game, researchers at UW can see more unique approaches to protein folding and gain a better understanding of it. (In case the link above doesn’t work, here it is again: http://www.gamesforchange.org/play/foldit/)

Have a great summer!

Vy