Come together, electrostatically, as one

How do 2 proteins come together to form a complex? Although we can sometimes determine the crystal structure of a complex, this only gives us a static picture, the end product of a dynamic process.

To provide a glimpse into how two proteins come together, Tang and co-workers, in the paper "Visualization of transient encounter complexes in protein–protein association" Nature (2006) 444:383, devised a brilliant scheme to capture the alternative ways that two proteins bind together in solution.

They studied the binding of the N-terminal domain of enzyme I (EIN) to the phosphocarrier protein (HPr). The figure on the left shows EIN on the left (mostly blue). HPr is the protein on the right (green). In the experiment, they attached Mn2+ ions (3 red balls on the far right) onto the surface of HPr.

The key idea is that these Mn2+ ions induce a magnetic response in EIN where the magnetic response (ΔΓ2) of the backbone H atoms in EIN depends on the distance of the H atoms from the Mn2+ ions. The magnetic response ΔΓ2 (red dots) for each backbone H atom in EIN is plotted below:



The black line in the figure above is the ΔΓ2 calculated from the crystal structure of the complex of EIN bound to HPr. The measured ΔΓ2 (red dots) show a number of peaks that deviate from the black line. These peaks correspond to transient binding sites of HPr to other parts of the EIN surface.

From the results of a series of similar experiments, Tang and co-workers reconstructed the most likely transient binding sites of HPr to EIN. The alternate conformations of HPr are shown as a density map (green) in the following image. The actual binding site of HPr in the crystal structure is shown in blue, and EIN is shown as an eletrostatic surface map (red is positive, white neutral, blue is negative):



The alternative conformations of HPr bind to positively charged parts of the surface of EIN. However, near the actual binding site, there are few alternate conformations, even though the surface around the actual binding site is also strongly charged.

Tang and co-workers conclude that it is very easy for two proteins to stick together, drawn by simple electrostatic attraction. But this binding is weak. To explain the absence of alternative conformations around the actual binding sites, they argue that once the HPr binds close to the actual binding site, there is a large energy funnel that forces the HPr into the actual binding site.

This is the first study to show, experimentally, that two proteins can transiently bind anywhere through electrostatic interaction, a truly significant result.

Looking at the surface of a membrane

What does the the membrane that wraps around our cells look like? We know that the membrane is choc-a-bloc full of proteins, but we can't see them directly because the level of detail is too small for our electron microscopes to look at, without destroying the cell.

Is there a way to re-construct the mosaic of proteins that normally stud a membrane? In "Molecular Anatomy of a Trafficking Organelle" Cell (2006) 127:831, Takamori and co-workers studied the synaptic vesicle - a little bubble wrapped up in membrane that carries neuro-transmitters from one synapse in the brain to another.

This is a synaptic vesicle as seen with electron microscopy. You can't go into any more detail. Instead, Takamori and co-workers determined the precise composition of all the proteins that float in the membrane of the synaptic vesicle. With this information, they built this delightful model of a synaptic vesicle:



This image is somewhat reminiscent of the vibrant watercolors painted by David Goodsell, which were created using some deep intuitions about protein density and oodles of artistic license:

How to tell if a relationship is over

Short film (90s) at depict.org. I learnt heaps.

The Outsider Chronicles

If I were to tell you that recently, I went to an experimental modern dance piece , you might raise your eyebrows. If I were to tell you that the piece explored trans-gender issues in a social activism festival, you might even start to smirk. And if I were tell you that it was brilliant, you would roll your eyes around and around until I could only see the whites of your eyes. Well, I went to, saw, and vastly enjoyed Sean Dorsey's "The Outsider Chronicles", as part of the ManiFestival (Dance Brigade's Festival for Social Change) in San Francisco.

"The Outsider Chronicles" is a loosely biographical collection of consists of 6 short pieces. The stories revolve around the theme of sexual identity. Before the show, I was a little afraid that this was going to be a niche piece. The audience was not your typical theater crowd, mainly lesbian couples and trans-gender folks. Would the piece speak in a secret code of the trans-gender community, impenetrable to the ears of an outsider? Fortunately this was not the case. "The Outsider Chronicles" spoke in a universal language. It spoke in the form of story.

The most significant artistic choice that Dorsey made, was to perform the dance pieces over a spoken word performance. I had never seen this fusion of spoken word and dance before. By engaging the audience through a series of beautifully written story, Dorsey had highlighted a fundamental problem with most forms of dance that I have seen - although kinetically enthralling, most dance is intellectually dis-engaging. To fully engage in a scene, I think it is imperative that we get under the skin of the characters on stage. Dance alone cannot tell such stories. With spoken word, character and dialog are refracted onto the movements on the stage.

The miracle of the "The Outsider Chronicles" is that Sean Dorsey is every bit as good a spoken-word performer as he is a dancer. There were six beautifully written stories, full of vigor, life and humor. There was a piece about the first time he kissed a girl. Another was a poignant piece about the drive of a couple to have an emergency meeting with his father. These spoken word pieces could easily stand on their own. Here, they formed the platform on which the dance unfolded.

The stories and the dance dove-tailed as we see flying bodies act out the conflicts and confusions of the relationships embedded in the stories. The spoken dialogue gave flesh to the movements. Movement and intention become one. I could felt the stories wash over me, kinetically, bodily. Reflecting on this, I realized that the vacuity of much of traditional ballet was due to the inherent limit of dance to convey rich emotional experience. Whereas seasoned ballet enthusiasts already know the story of the ballet that they will see, and hence can interpret the actions on the stage, there is no such recourse for a novice. In "The Outsider Chronicles", Dorsey cuts through that incomprehensibility by merging voice with dance.

I was also enthralled by the lighting and staging. The staging was spare, allowing the rather imaginative use of light to cut through the space. Slabs of light were used to conjure up a conjugal bed, another to project the interior of a car free-wheeling on a road-trip. In another scene, a wash of vertical light conjured up a bath-room on the front of the stage.

Dorsey examines the line from desire to the fulfillment of a fully-realized self-identity. His stories document his struggle to engage with the world, though specific to trans-gender issues, there is a universal dimension to his story. The strength and compassion in the way he recounts his past, makes his struggle heroic. In the last piece "Creativity", Dorsey laments a moment in his youth where he missed a chance to seize the moment and declare himself, and pit himself against everyone around him. But if he failed in that moment in the past, he has more than made-up for it in sublimating his story into a muscular work of art.

The Penguin who Goes Shopping

I know the cute factor to this video will drip through your computer screen and onto the carpet. But I really, I couldn't resist posting the daily adventures of penguin shopper, Lala-chan:

Credentials to run a South American country

I was just reading about Verónica Michelle Bachelet Jeria, the current president of Chile. Her biography is phenomenal (from wikipedia):

Bachelet—a surgeon, pediatrician and epidemiologist with studies in military strategy—served as Health Minister and Defense Minister under President Ricardo Lagos. She is a separated mother of three and a self-described agnostic, which sets her apart in a predominantly conservative and Catholic country. A polyglot, she speaks Spanish, English, German, Portuguese and French.

How could anyone so talented become the head of state of any nation?