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SCIENTIFIC LITERATURE · MED

A cryo-electron microscopic approach to elucidate protein structures from human brain microsomes.

Life Sci Alliance · 2022-11-30

DOI: 10.26508/lsa.202201724PMID: 36450447

Open accessresearch-article; Journal Article; Research Support, N.I.H., ExtramuralOriginal source ↗

Research overview

The text below is the source article’s original abstract under a verified reuse license. cc by

We recently developed a "Build and Retrieve" cryo-electron microscopy (cryo-EM) methodology, which is capable of simultaneously producing near-atomic resolution cryo-EM maps for several individual proteins from a heterogeneous, multiprotein sample. Here we report the use of "Build and Retrieve" to define the composition of a raw human brain microsomal lysate. From this sample, we simultaneously identify and solve cryo-EM structures of five different brain enzymes whose functions affect neurotransmitter recycling, iron metabolism, glycolysis, axonal development, energy homeostasis, and retinoic acid biosynthesis. Interestingly, malfunction of these important proteins has been directly linked to several neurodegenerative disorders, such as Alzheimer's, Huntington's, and Parkinson's diseases. Our work underscores the importance of cryo-EM in facilitating tissue and organ proteomics at the atomic level.

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