Disulfide Bridge Formation in the Crystalline Lens

Article: How the 3-D structure of eye-lens proteins is formed
Source: Goethe University (Germany), via ScienceDaily  and Technology Networks
Published: February 10, 2021

Side view of a ribosomal 50S subunit with a focus on the nascent chain

Researchers at Goethe University in Germany are taking a basic science approach to study the protein structure of the crystalline lens using a genetically modified bacterial model. In particular, they studied the disulfide bridges, bonds between two sulfur-containing amino acids, in βγ-crystallins. Where this is interesting from a molecular standpoint is that disulfide bonds are not easy for the cell to produce and maintain given a cellular environment that promotes their dissolution. In the finished βγ-crystallin protein, these bonds are shielded from the cellular environment by placement in the internal parts of the protein. But while the protein is in the process of formation, this is not yet possible. It had been previously assumed that because the ribosomal tunnel is too narrow, disulfide bridges could only form after protein formation was completed. The researchers tested this assumption on their bacterial model using various spectroscopic techniques and theoretical simulations. They found that disulfide bridges are already formed during the synthesis of the amino acid chain, that is, within the ribosomal tunnel. One of the researchers notes, "Surprisingly, however, these are not the same disulphide bridges that are later present in the finished gamma-B crystallin. We conclude that at least some of the disulphide bridges are later dissolved again and linked differently," and that perhaps the preliminary disulfide bridges accelerate the formation of the final disulfide bridges when the protein is released from the ribosome. The focus and weight of this study in the basic sciences, and in a very restricted aspect of crystalline protein formation, limit its application in clinical settings. Nonetheless, the crystalline lens is a structure with ubiquitous impact, the transparency and power of the eye being due in large part to the packing of these crystallin proteins in the lens (with the nuance that the major refractive component of the eye is the cornea). Study of crystalline lens formation thus informs the progression of cataracts and could aid in research toward their prevention.

My rating of this study: ⭐⭐

Schulte L, Mao J, Reitz J, et al. "Cysteine oxidation and disulfide formation in the ribosomal exit tunnel." Nature Communications.  11(5569). 4 November 2020. https://doi.org/10.1038/s41467-020-19372-x