The Humble Phosphate Ion: Making Life “Go”

Author: John Charpentier

Editors; Noah Steinfeld, Tricia Garay, and Scott Barolo

A glance into any organic chemistry or biochemistry textbook reveals a dizzying variety of chemical compounds, reactions and mechanisms. It is not at all obvious why one particular class of reaction, the attachment and detachment of a phosphate group (PO43-) to molecules like nucleotides and proteins, is central to making the chemistry of life “go.”

Proteins: Not Just for Getting Swole, Brah

Figure 1. A phosphate ion. Note the negative charges.

Proteins are the working-class heroes of the cell: they get things done. A protein’s function is largely determined by its shape, which in turn is dictated by the linear sequence of chemically distinct amino acid subunits it is composed of. The rules of protein folding are astonishingly complex. Generally speaking, the reluctance of hydrophobic (“water-fearing”) amino acids to project outward into the watery cytoplasm is the primary determinant of protein shape, but electrostatic interactions between amino acid residues are also important. Phosphate groups have three negative charges, which means that when they are linked to or removed from a protein by specialized enzymes, they can dramatically modify its shape and stability, and therefore its function. The phosphorylation/dephosphorylation cycle operates like a switch to regulate protein behavior: add a phosphate and you get a violent Mr. Hyde protein; take it off and you get the amiable Dr. Jekyll.


Figure 2. Cellular homunculi don’t exist – decisions are made by integrating signaling inputs from the environment to effect changes in gene expression.

So where do we find phosphorylation in biochemistry? The answer is: pretty much everywhere! I will discuss two key examples. Firstly, phosphorylation is important in “cell signaling,” the sensing of messages from outside a cell and their incorporation into cellular decision-making. It’s worth observing that there isn’t anything we’d recognize as a brain in cells – decision-making is an emergent property of the integration of these signals, not the doing of a microscopic cellular homunculus pulling levers or “thinking.”

Continue reading “The Humble Phosphate Ion: Making Life “Go””

Analyzing without Lysing: Non-Damaging Techniques for Monitoring Cells

Author: Sarah Kearns

Editors: Whit Froehlich, Ada Hagan, and Irene Park

The interior of a cell is inherently complex with a myriad of processes going on all at once. Despite the clean images that are commonly shown in diagrams and textbooks, the parts inside are more of a whirlwind of structural components, proteins, and products (see Figure 1).

Figure 1. Left is a cartoon image of a whole cell highlighting the different organelles (cellular compartments). Right is a computer simulation of the cytoplasm, the fluid between organelles. There are thousands of chemical processes going on within it.

Continue reading “Analyzing without Lysing: Non-Damaging Techniques for Monitoring Cells”

Computing Levinthal’s Paradox: Protein Folding, Part 2

Author: Sarah Kearns

Editors: David Mertz, Zuleirys Santana Rodriguez, and Scott Barolo

In a previous post, we discussed how proteins fold into unique shapes that allow them to perform their biological functions. Through many physical and chemical properties, like hydrogen bonding and hydrophobicity, proteins are able to fold correctly. However, proteins can fold improperly, and sometimes these malformed peptides aggregate, leading to diseases like Alzheimer’s.

How can we figure out when the folding process goes wrong? Can we use computers to figure out the folding/misfolding process and develop methods to prevent or undo the damage done by protein aggregates?

Continue reading “Computing Levinthal’s Paradox: Protein Folding, Part 2”

How to Fold (and Misfold) a Protein (Part 1)

Author: Sarah Kearns

Editors: David Mertz, Zulierys Santana-Rodriguez, and Scott Barolo

Proteins do most of the work in your body: Depending on their shape, they can digest your food, fire your neurons, give color to your eyes and allow you to see colors. Proteins follow instructions encoded in your DNA to fold into their shape, but how do they “know” what shape to fold into to perform their biological functions? What happens when they fold incorrectly?

Continue reading “How to Fold (and Misfold) a Protein (Part 1)”