Solution structure of a CUE-ubiquitin complex reveals a conserved mode of ubiquitin binding.
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.
Kang
Richard S
RS
Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, IL 60208, USA.
Daniels
Cynthia M
CM
Francis
Smitha A
SA
Shih
Susan C
SC
Salerno
William J
WJ
Hicke
Linda
L
Radhakrishnan
Ishwar
I
D020816:Amino Acid Motifs / Q000502:physiology; D000595:Amino Acid Sequence / Q000502:physiology; D001665:Binding Sites / Q000502:physiology; D002352:Carrier Proteins / Q000737:chemistry*; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin / Q000737:chemistry*
C109280:CUE1 protein, S cerevisiae; D002352:Carrier Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin