The use of an integrated systems biology approach to investigate tissues and organs has been thought to be impracticable in the field of structural biology, where the techniques mainly focus on determining the structure of a particular biomacromolecule of interest.
In an article published in Cell Reports in late December, a research team led by Edward Yu, professor of pharmacology, reported the use of cryo-electron microscopy (cryo-EM) to define the composition of a raw bovine retinal pigment epithelium (RPE) lysate.
From this sample, the researchers simultaneously identified and solved cryo-EM structures of seven different RPE enzymes whose functions affect neurotransmitter recycling, iron metabolism, gluconeogenesis, glycolysis, axonal development and energy homeostasis. Dysfunction of these important proteins has been directly linked to several neurodegenerative disorders, including Huntington’s disease, amyotrophic lateral sclerosis (ALS), Parkinson’s disease, Alzheimer’s disease and schizophrenia.
The researchers’ work underscores the importance of cryo-EM in facilitating tissue and organ proteomics at the atomic level.