Solution structure of a CUE-ubiquitin complex reveals a conserved mode of ubiquitin binding

Richard S. Kang; Cynthia M. Daniels; Smitha A. Francis; Susan C. Shih; William J. Salerno; Linda Hicke; Ishwar Radhakrishnan

doi:10.1016/S0092-8674(03)00362-3

Solution structure of a CUE-ubiquitin complex reveals a conserved mode of ubiquitin binding

Richard S. Kang, Cynthia M. Daniels, Smitha A. Francis, Susan C. Shih, William J. Salerno, Linda Hicke, Ishwar Radhakrishnan^*

^*Corresponding author for this work

Robert H. Lurie Comprehensive Cancer Center

Research output: Contribution to journal › Article › peer-review

205 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	621-630
Number of pages	10
Journal	Cell
Volume	113
Issue number	5
DOIs	https://doi.org/10.1016/S0092-8674(03)00362-3
State	Published - May 30 2003

Funding

We thank Kurt Swanson, Sam Seaver, and Ben Ramirez for discussions. The pET-3a and pMCSG7 vectors were generous gifts from Cecile Pickart (Johns Hopkins) and Frank Collart (Argonne National Laboratory), respectively. This work was supported by funds from the NIH to I.R. and L.H. C.M.D. was supported by an IMGIP predoctoral fellowship. We gratefully acknowledge the Lurie Comprehensive Cancer Center for supporting the Structural Biology Center at Northwestern and the Keck Biophysics Facility at Northwestern for access to instrumentation ( www.biochem.northwestern.edu/Keck/keckmain.html ).

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/S0092-8674(03)00362-3

Cite this

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title = "Solution structure of a CUE-ubiquitin complex reveals a conserved mode of ubiquitin binding",

abstract = "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.",

author = "Kang, {Richard S.} and Daniels, {Cynthia M.} and Francis, {Smitha A.} and Shih, {Susan C.} and Salerno, {William J.} and Linda Hicke and Ishwar Radhakrishnan",

note = "Funding Information: We thank Kurt Swanson, Sam Seaver, and Ben Ramirez for discussions. The pET-3a and pMCSG7 vectors were generous gifts from Cecile Pickart (Johns Hopkins) and Frank Collart (Argonne National Laboratory), respectively. This work was supported by funds from the NIH to I.R. and L.H. C.M.D. was supported by an IMGIP predoctoral fellowship. We gratefully acknowledge the Lurie Comprehensive Cancer Center for supporting the Structural Biology Center at Northwestern and the Keck Biophysics Facility at Northwestern for access to instrumentation ( www.biochem.northwestern.edu/Keck/keckmain.html ). ",

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AU - Salerno, William J.

AU - Hicke, Linda

AU - Radhakrishnan, Ishwar

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PY - 2003/5/30

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N2 - 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.

AB - 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.

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Solution structure of a CUE-ubiquitin complex reveals a conserved mode of ubiquitin binding

Abstract

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