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electron microscopy

Snapshots of Life: New Target for Herpes Treatment?

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HSV-1Something about this image reminds me of that wacky and infectious old song: “It was a one-eyed, one-horned, flyin’ purple people eater …” Of course, this purple blob isn’t a people eater, but it does happen to be infectious. What you see here is a 3D rendering of a protein that the herpes simplex virus 1 (HSV-1)—one of two herpes viruses that cause genital herpes and cold sores—depends upon to infect human cells.

When a cell is infected with HSV-1, the virus inserts its DNA into human cells, periodically coming out of dormancy to make more copies of itself. However, errors sometimes occur when the DNA is replicated. When that happens, an HSV-1 protein, dubbed infected cell protein 8 (ICP8), stitches broken pieces of DNA back together. That’s what you see depicted in this schematic, which shows two single strands of DNA (red with multicolor bases) entering an ICP8 complex (purplish blue) to be reannealed into DNA’s familiar double-stranded helix (red).


Protein Machines at Work

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This video shows a molecular view of the reactions that take place inside the pyruvate dehydrogenase complex, a protein machine found in the cell’s powerhouse, the mitochondria. 3D imaging of this machine by high-resolution electron microscopy reveals how the different components essential for the reaction are organized. Watch the flexible arms move inside the protein machine as pyruvate (an essential compound made from glucose) gets converted into acetyl-CoA (a precursor to the cell’s energy supply).

Credit: Jacqueline Milne and Sriram Subramaniam, Laboratory of Cell Biology, National Cancer Institute; Donald Bliss, National Library of Medicine; NIH

References:

Molecular architecture and mechanism of an icosahedral pyruvate dehydrogenase complex: a multifunctional catalytic machine. Milne JL, Shi D, Rosenthal PB, Sunshine JS, Domingo GJ, Wu X, Brooks BR, Perham RN, Henderson R, Subramaniam S. EMBO J. 2002 Nov 1;21(21):5587-98.

Molecular structure of a 9-MDa icosahedral pyruvate dehydrogenase subcomplex containing the E2 and E3 enzymes using cryoelectron microscopy. Milne JL, Wu X, Borgnia MJ, Lengyel JS, Brooks BR, Shi D, Perham RN, Subramaniam S. J Biol Chem. 2006 Feb 17;281(7):4364-70.

Extended polypeptide linkers establish the spatial architecture of a pyruvate dehydrogenase multienzyme complex. Lengyel JS, Stott KM, Wu X, Brooks BR, Balbo A, Schuck P, Perham RN, Subramaniam S, Milne JL. Structure. 2008 Jan;16(1):93-103

 


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