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TitleA cryo-electron microscopic approach to elucidate protein structures from human brain microsomes.
Journal, issue, pagesLife Sci Alliance, Vol. 6, Issue 2, Year 2023
Publish dateNov 30, 2022
AuthorsMarios L Tringides / Zhemin Zhang / Christopher E Morgan / Chih-Chia Su / Edward W Yu /
PubMed AbstractWe 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 ...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.
External linksLife Sci Alliance / PubMed:36450447 / PubMed Central
MethodsEM (single particle)
Resolution2.69 - 3.4 Å
Structure data

27574

8dnm

EMDB-27574, PDB-8dnm:
Human Brain Dihydropyrimidinase-related protein 2
Method: EM (single particle) / Resolution: 2.76 Å

27575

8dno

EMDB-27575, PDB-8dno:
Human Brain Aldehyde Dehydrogenase 1 family, member A1
Method: EM (single particle) / Resolution: 3.4 Å

27576

8dnp

EMDB-27576, PDB-8dnp:
Human Brain Ferritin Heavy Chain
Method: EM (single particle) / Resolution: 2.69 Å

27579

8dns

EMDB-27579, PDB-8dns:
Human Brain Glyceraldehyde 3-phosphate dehydrogenase
Method: EM (single particle) / Resolution: 3.22 Å

27580

8dnu

EMDB-27580, PDB-8dnu:
Human Brain Glutamine Synthetase
Method: EM (single particle) / Resolution: 2.73 Å

Chemicals

ChemComp-FE:
Unknown entry / Iron

ChemComp-MN:
Unknown entry

Source
  • homo sapiens (human)
  • human (human)
KeywordsHYDROLASE / human brain / DPYSL2 / OXIDOREDUCTASE / ALDH1A1 / METAL BINDING PROTEIN / ferritin / heavy chain / GAPDH / LIGASE / Glutamine Synthetase

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