Structural Basis for Ubiquitin Recognition by SH3 Domains

Yuan He; Linda Hicke; Ishwar Radhakrishnan

doi:10.1016/j.jmb.2007.07.074

Structural Basis for Ubiquitin Recognition by SH3 Domains

Yuan He, Linda Hicke, Ishwar Radhakrishnan^*

^*Corresponding author for this work

Molecular Biosciences

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

30 Scopus citations

Abstract

The SH3 domain is a protein-protein interaction module commonly found in intracellular signaling and adaptor proteins. The SH3 domains of multiple endocytic proteins have been recently implicated in binding ubiquitin, which serves as a signal for diverse cellular processes including gene regulation, endosomal sorting, and protein destruction. Here we describe the solution NMR structure of ubiquitin in complex with an SH3 domain belonging to the yeast endocytic protein Sla1. The ubiquitin binding surface of the Sla1 SH3 domain overlaps substantially with the canonical binding surface for proline-rich ligands. Like many other ubiquitin-binding motifs, the SH3 domain engages the Ile44 hydrophobic patch of ubiquitin. A phenylalanine residue located at the heart of the ubiquitin-binding surface of the SH3 domain serves as a key specificity determinant. The structure of the SH3-ubiquitin complex explains how a subset of SH3 domains has acquired this non-traditional function.

Original language	English (US)
Pages (from-to)	190-196
Number of pages	7
Journal	Journal of Molecular Biology
Volume	373
Issue number	1
DOIs	https://doi.org/10.1016/j.jmb.2007.07.074
State	Published - Oct 12 2007

Funding

We thank Hisae Matsuura and Richard Kang for the initial development of the project, Yongbo Zhang for assistance with NMR data collection, the NIH for grant support to L.H. and I.R. and the Lurie Cancer Center for supporting structural biology research at Northwestern. I.R. is a Scholar of the Leukemia and Lymphoma Society.

Keywords

SH3
endocytosis
monoubiquitin signaling
protein-protein interactions
ubiquitin-binding motif

ASJC Scopus subject areas

Molecular Biology
Structural Biology

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10.1016/j.jmb.2007.07.074

Cite this

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title = "Structural Basis for Ubiquitin Recognition by SH3 Domains",

abstract = "The SH3 domain is a protein-protein interaction module commonly found in intracellular signaling and adaptor proteins. The SH3 domains of multiple endocytic proteins have been recently implicated in binding ubiquitin, which serves as a signal for diverse cellular processes including gene regulation, endosomal sorting, and protein destruction. Here we describe the solution NMR structure of ubiquitin in complex with an SH3 domain belonging to the yeast endocytic protein Sla1. The ubiquitin binding surface of the Sla1 SH3 domain overlaps substantially with the canonical binding surface for proline-rich ligands. Like many other ubiquitin-binding motifs, the SH3 domain engages the Ile44 hydrophobic patch of ubiquitin. A phenylalanine residue located at the heart of the ubiquitin-binding surface of the SH3 domain serves as a key specificity determinant. The structure of the SH3-ubiquitin complex explains how a subset of SH3 domains has acquired this non-traditional function.",

keywords = "SH3, endocytosis, monoubiquitin signaling, protein-protein interactions, ubiquitin-binding motif",

author = "Yuan He and Linda Hicke and Ishwar Radhakrishnan",

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AU - Radhakrishnan, Ishwar

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N2 - The SH3 domain is a protein-protein interaction module commonly found in intracellular signaling and adaptor proteins. The SH3 domains of multiple endocytic proteins have been recently implicated in binding ubiquitin, which serves as a signal for diverse cellular processes including gene regulation, endosomal sorting, and protein destruction. Here we describe the solution NMR structure of ubiquitin in complex with an SH3 domain belonging to the yeast endocytic protein Sla1. The ubiquitin binding surface of the Sla1 SH3 domain overlaps substantially with the canonical binding surface for proline-rich ligands. Like many other ubiquitin-binding motifs, the SH3 domain engages the Ile44 hydrophobic patch of ubiquitin. A phenylalanine residue located at the heart of the ubiquitin-binding surface of the SH3 domain serves as a key specificity determinant. The structure of the SH3-ubiquitin complex explains how a subset of SH3 domains has acquired this non-traditional function.

AB - The SH3 domain is a protein-protein interaction module commonly found in intracellular signaling and adaptor proteins. The SH3 domains of multiple endocytic proteins have been recently implicated in binding ubiquitin, which serves as a signal for diverse cellular processes including gene regulation, endosomal sorting, and protein destruction. Here we describe the solution NMR structure of ubiquitin in complex with an SH3 domain belonging to the yeast endocytic protein Sla1. The ubiquitin binding surface of the Sla1 SH3 domain overlaps substantially with the canonical binding surface for proline-rich ligands. Like many other ubiquitin-binding motifs, the SH3 domain engages the Ile44 hydrophobic patch of ubiquitin. A phenylalanine residue located at the heart of the ubiquitin-binding surface of the SH3 domain serves as a key specificity determinant. The structure of the SH3-ubiquitin complex explains how a subset of SH3 domains has acquired this non-traditional function.

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KW - ubiquitin-binding motif

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Structural Basis for Ubiquitin Recognition by SH3 Domains

Abstract

Funding

Keywords

ASJC Scopus subject areas

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Solution Structure of the Sla1 SH3-3-Ubiquitin Complex

Cite this

Structural Basis for Ubiquitin Recognition by SH3 Domains

Abstract

Funding

Keywords

ASJC Scopus subject areas

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Other files and links

Fingerprint

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Solution Structure of the Sla1 SH3-3-Ubiquitin Complex

Cite this