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J Mol Biol. 2001 Feb 23;306(3):527-37.

Solution structure of Grb2 reveals extensive flexibility necessary for target recognition.

Author information

1
Department of Structural Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, 060-0812, Japan.

Abstract

Grb2 is an adaptor protein composed of a single SH2 domain flanked by two SH3 domains. Grb2 functions as an important evolutionary conserved link between a variety of cell membrane receptors and the Ras/MAP kinase-signaling cascade. Here, we describe the solution structure of Grb2 as revealed by NMR and small angle X-ray scattering measurements. We demonstrate that Grb2 is a flexible protein in which the C-terminal SH3 domain is connected to the SH2 domain via a flexible linker. This is in contrast to the previously described Grb2 crystal structure, which showed a compact structure with intramolecular contact between two SH3 domains. Binding experiments on Grb2 and peptides containing two different proline-rich sequences indicate that Grb2 adapts the relative position and orientation of the two SH3 domains to bind bivalently to the target peptide sequences.

PMID:
11178911
DOI:
10.1006/jmbi.2000.4396
[Indexed for MEDLINE]

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