@article {3095169,
	title = {Exposure of bipartite hydrophobic signal triggers nuclear quality control of Ndc10 at the endoplasmic reticulum/nuclear envelope.},
	journal = {Mol Biol Cell},
	volume = {22},
	year = {2011},
	month = {2011 Dec},
	pages = {4726-39},
	abstract = {Proper functioning of the protein-folding quality control network depends on the network{\textquoteright}s ability to discern diverse structural perturbations to the native states of its protein substrates. Despite the centrality of the detection of misfolded states to cell home-ostasis, very little is known about the exact sequence and structural features that mark a protein as being misfolded. To investigate these features, we studied the requirements for the degradation of the yeast kinetochore protein Ndc10p. Mutant Ndc10p is a substrate of a protein-folding quality control pathway mediated by the E3 ubiquitin (Ub) ligase Doa10p at the endoplasmic reticulum (ER)/nuclear envelope membrane. Analysis of Ndc10p mutant derivatives, employing a reverse genetics approach, identified an autonomous quality control-associated degradation motif near the C-terminus of the protein. This motif is composed of two indispensable hydrophobic elements: a hydrophobic surface of an amphipathic helix and a loosely structured hydrophobic C-terminal tail. Site-specific point mutations expose these elements, triggering ubiquitin-mediated and HSP70 chaperone-dependent degradation of Ndc10p. These findings substantiate the ability of the ER quality control system to recognize subtle perturbation(s) in the native structure of a nuclear protein.},
	keywords = {Amino Acid Motifs, DNA-Binding Proteins, Endoplasmic Reticulum, HSP70 Heat-Shock Proteins, Hydrophobic and Hydrophilic Interactions, Kinetochores, Mutation, Nuclear Envelope, Protein Folding, Protein Structure, Tertiary, Proteolysis, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Ubiquitin-Protein Ligases},
	author = {Furth, Noa and Gertman, Or and Shiber, Ayala and Alfassy, Omri S and Cohen, Itamar and Rosenberg, Masha M and Doron, Nurit Kleinberger and Assaf Friedler and Ravid, Tommer}
}
