TY - JOUR
T1 - Structural Basis for Ubiquitin Recognition by SH3 Domains
AU - He, Yuan
AU - Hicke, Linda
AU - Radhakrishnan, Ishwar
N1 - Funding Information:
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.
PY - 2007/10/12
Y1 - 2007/10/12
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.
KW - SH3
KW - endocytosis
KW - monoubiquitin signaling
KW - protein-protein interactions
KW - ubiquitin-binding motif
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U2 - 10.1016/j.jmb.2007.07.074
DO - 10.1016/j.jmb.2007.07.074
M3 - Article
C2 - 17765920
AN - SCOPUS:34548564106
SN - 0022-2836
VL - 373
SP - 190
EP - 196
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 1
ER -