How enzymes in the cell membrane add grease to other cellular proteins
In humans, there are 23 enzymes embedded in the cell membrane that belong to the DHHC family of protein acyltransferases, a group of enzymes that link a certain type of fat molecule to other proteins in the cell. This process, known as protein palmitoylation, affects an estimated 1,000 cellular proteins. However, there was no understanding of the three-dimensional structure and mechanism of the DHHC family of enzymes.
IRP researchers, led by Anirban Banerjee, Ph.D., undertook the challenge of determining the high-resolution atomic structure of two different DHHC proteins, DHHC15 and DHHC20. Using a clever experimental trick, the team also uncovered the structure of human DHHC20 when it is linked to a fat molecule, a development which offers insights into how DHHC enzymes bind to fat molecules before latching onto other proteins.
Protein palmitoylation impacts a wide range of physiological processes and DHHC enzymes have been linked to a number of diseases, particularly neuropsychiatric diseases and cancer. Determining the structures of DHHC enzymes provides a starting point for understanding how they work and developing methods of making them more or less active. Knowledge of DHHC enzyme structure also allows the development of molecular tools that could aid drug discovery for diseases like breast cancer.
Rana MS, Kumar P, Lee CJ, Verardi R, Rajashankar KR, Banerjee A. (2018). Fatty acyl recognition and transfer by an integral membrane S-acyltransferase. Science. Jan 12;359(6372).