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

Autor:	Tringides ML; Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Zhang Z; Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Morgan CE; Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Su CC; Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Yu EW; Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH, USA edward.w.yu@case.edu.
Jazyk:	angličtina
Zdroj:	Life science alliance [Life Sci Alliance] 2022 Nov 30; Vol. 6 (2). Date of Electronic Publication: 2022 Nov 30 (Print Publication: 2023).
DOI:	10.26508/lsa.202201724
Abstrakt:	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. (© 2022 Tringides et al.)
Databáze:	MEDLINE
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