Breaking news on how ubiquitin regulates intracellular transport

Camilla Raiborg

Camilla Raiborg, a postdoc of the Norwegian Cancer Society working in Harald Stenmark's group at the Department of Biochemistry of the Institute for Cancer Research, has recently published two articles together with international collaborators that reveal how the small protein ubiquitin regulates intracellular trafficking.

The first article, published in Nature Cell Biology in collaboration with the group of Ivan Dikic at the Goethe University in Frankfurt, shows that the protein machinery that controls intracellular transport (labelled red in the figure from the article) is regulated by mono-ubiquitin. Proteins such as Eps15 and Hrs function by sorting ubiquitinated membrane proteins for endocytosis and endosome-lysosome transport, respectively. The article in Nature Cell Biology (journal impact factor = 20.35) shows that mono-ubiquitination of these sorting proteins cause them to bind their "own" ubiquitin moiety instead of interacting with ubiquitinated cargo (black), and this ubiquitination of the sorting machinery has thus a negative regulatory function in intracellular protein trafficking.

The second article, published in Nature Structural and Molecular Biology (journal impact factor = 12.0) in collaboration with the group of Soichi Wakatsuki at the Photon Factory in Ibaraki, Japan, shows how Hrs binds to ubiquitin. The crystal structure of a complex between the ubiquitin-binding motif of Hrs and ubiquitin shows that the ubiquitin-binding motif (red in the figure from the article) is a symmetric helix that is able to bind two ubiquitin molecules simultaneously (labelled in blue and green, respectively). Cellular studies show that the ability to bind two ubiquitin molecules is critical for the function of Hrs in sorting of endocytosed growth factor receptors. This explains how Hrs can bind multi-ubiquitinated membrane proteins even if the affinity between Hrs and a single ubiquitin molecule is low.

Links:

New articles revealing how the small protein ubiquitin regulates intracellular trafficking:

Double-sided ubiquitin binding of Hrs-UIM in endosomal protein sorting - published in Nature Structural & Molecular Biology (2006) (journal impact factor: 12.0)

Regulation of ubiquitin-binding proteins by monoubiquitination - published in Nature Cell Biology (2006) (journal impact factor: 20.35)

Harald Stenmark's group

Feb 6, 2006 [5693 visits]

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