Solution Structure of a CUE-Ubiquitin Complex Reveals a Conserved Mode of Ubiquitin Binding

• Published in: Cell Vol. 113; no. 5; pp. 621 - 630
• Main Authors: Kang, Richard S, Daniels, Cynthia M, Francis, Smitha A, Shih, Susan C, Salerno, William J, Hicke, Linda, Radhakrishnan, Ishwar
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.05.2003
• Subjects: Amino Acid Motifs - physiology; Amino Acid Sequence - physiology; Binding Sites - physiology; Carrier Proteins - chemistry; Macromolecular Substances; Membrane Proteins - chemistry; Models, Molecular; Molecular Sequence Data; Protein Binding - physiology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins; Ubiquitin - chemistry
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(03)00362-3

Monoubiquitination serves as a regulatory signal in a variety of cellular processes. Monoubiquitin signals are transmitted by binding to a small but rapidly expanding class of ubiquitin binding motifs. Several of these motifs, including the CUE domain, also promote intramolecular monoubiquitination. The solution structure of a CUE domain of the yeast Cue2 protein in complex with ubiquitin reveals intermolecular interactions involving conserved hydrophobic surfaces, including the Leu8-Ile44-Val70 patch on ubiquitin. The contact surface extends beyond this patch and encompasses Lys48, a site of polyubiquitin chain formation. This suggests an occlusion mechanism for inhibiting polyubiquitin chain formation during monoubiquitin signaling. The CUE domain shares a similar overall architecture with the UBA domain, which also contains a conserved hydrophobic patch. Comparative modeling suggests that the UBA domain interacts analogously with ubiquitin. The structure of the CUE-ubiquitin complex may thus serve as a paradigm for ubiquitin recognition and signaling by ubiquitin binding proteins.