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Protein Folding In The Hands Of AI

Written and illustrated by: Jacquelyn Roberts

Edited by: Jennifer Baker and Christina Del Greco

“Structure implies function” is a phrase often repeated by biochemists to describe how molecular machines work in the body. For a protein, structure is formed as its string of amino acids twists and folds into a globular final form. If amino acids are beads on a string, then the folded protein is the final necklace or finished work. This “final form” lends clues to the protein’s role in the cell. Often, like a lock and key, proteins and their chemical partners ft together perfectly. But for a long time, we had absolutely no idea how or why proteins reproducibly twist and fold in the same way every time to adopt a consistent final form.

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Injectisomes: the hypodermic needles of bacteria

Written and illustrated by: Jacquelyn Roberts

Edited by: Sarah Bassiouni, Sophia Hill, Austin Shannon, and Madeline Barron

Pathogenic bacteria like Salmonella, Shigella, Yersinia, and Escherichia coli can inject proteins into target cells with an extremely small hypodermic needle called a type III secretion system, or T3SS. The injected proteins are called “effector proteins”, as they elicit effects in the host (in this case human) cell. The cell membranes of both the bacteria and host cell prevent large molecules like effector proteins from simply drifting inside, so bacteria need specialized delivery systems like the T3SS to do it. These specialized delivery systems are very similar to a syringe and needle, and have been nicknamed injectisomes (Figure 1). However, injectisomes are 10 million times smaller than the average syringe. In addition to being incredibly small, these syringes are extremely specific in the cargo that they accept for transport. Bacteria generally use these machines to inject effector proteins  that weaken the host cell, leading to easier bacterial infection. The mechanistic details of these molecular machines is of great interest to scientists for many reasons. Designing a specific inhibitor of the injectisome could render pathogenic bacteria harmless. On the other hand, engineering an injectisome for drug delivery could provide targeted biologic medicine to specific cells in the body.

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