Method Review: A Closer Look at Cryo-EM’s Impact on Dermatology

Key Takeaways

• Cryogenic electron microscopy (cryo-EM) enables high-resolution visualization of skin-related macromolecules under physiological conditions.
• Cryo-EM has helped uncover mechanisms of key dermatological treatments, such as sarecycline for acne and receptor-targeting therapies for chronic itch.
• The establishment of national cryo-EM centers is one approach being used to combat barriers to access and spread adoption. 

A recent method review in the Journal of Investigative Dermatology points to the potential of cryogenic electron microscopy (cryo-EM) in dermatological research.

According to the authors, advanced imaging technology enables atomic-resolution visualization of macromolecules in their native states, providing invaluable insights into the structure and function of proteins, macromolecular complexes, and other key components relevant to skin biology and diseases. The guide emphasized the advantages of cryo-EM, including its ability to bypass the limitations of X-ray crystallography by requiring smaller samples and no crystal growth. This makes it particularly suited for examining complex biological systems, such as keratinocyte proteins, desmosomes, and potential drug targets in skin disorders.

Specific applications in dermatology, according to the article, include the analysis of Cutibacterium acnes ribosomes, where cryo-EM revealed dual binding sites for the antibiotic sarecycline (providing understanding of its narrow-spectrum activity). The authors also noted that cryo-EM has shed light on the structural mechanisms underlying chronic itch by resolving the atomic details of Mas-related G-protein-coupled receptors (MRGPRs), which could be important in the development of targeted therapies for non-histaminergic pruritus.

Although technology-associated challenges such as high cost and specialized training requirements continue to be a factor, the authors noted that the establishment of national cryo-EM centers is facilitating broader access. The review calls on dermatology researchers to integrate cryo-EM into their investigative approaches.

"In the field of dermatology, access to cryo-EM will benefit researchers focused on large macromolecular complexes, such as desmosomes, IFs and other cytoskeleton machinery, proteins and protein complexes involved in keratinocyte differentiation, as well as proteins that can be potential drug targets," the authors concluded. "Using cryo-EM in dermatology in collaboration with biotechnology and pharmaceutical industries will enhance the development of targeted drugs that can alleviate human skin diseases.

Lomakin I, et al. Source: Journal of Investigative Dermatology. 2024. Doi:10.1016/j.jid.2024.10.594