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Acta Crystallogr Sect F Struct Biol Cryst Commun. 2010 Dec 1;66(Pt 12):1567-71. doi: 10.1107/S1744309110041333. Epub 2010 Nov 16.

Structure of the iSH2 domain of human phosphatidylinositol 3-kinase p85β subunit reveals conformational plasticity in the interhelical turn region.

Author information

1
Center for Advanced Biotechnology and Medicine, Department of Molecular Biology and Biochemistry, and Northeast Structural Genomics Consortium, Rutgers, The State University of New Jersey, 679 Hoes Lane, Piscataway, NJ 08854, USA.

Abstract

Phosphatidylinositol 3-kinase (PI3K) proteins actively trigger signaling pathways leading to cell growth, proliferation and survival. These proteins have multiple isoforms and consist of a catalytic p110 subunit and a regulatory p85 subunit. The iSH2 domain of the p85β isoform has been implicated in the binding of nonstructural protein 1 (NS1) of influenza A viruses. Here, the crystal structure of human p85β iSH2 determined to 3.3 Å resolution is reported. The structure reveals that this domain mainly consists of a coiled-coil motif. Comparison with the published structure of the bovine p85β iSH2 domain bound to the influenza A virus nonstructural protein 1 indicates that little or no structural change occurs upon complex formation. By comparing this human p85β iSH2 structure with the bovine p85β iSH2 domain, which shares 99% sequence identity, and by comparing the multiple conformations observed within the asymmetric unit of the bovine iSH2 structure, it was found that this coiled-coil domain exhibits a certain degree of conformational variability or `plasticity' in the interhelical turn region. It is speculated that this plasticity of p85β iSH2 may play a role in regulating its functional and molecular-recognition properties.

PMID:
21139197
PMCID:
PMC2998356
DOI:
10.1107/S1744309110041333
[Indexed for MEDLINE]
Free PMC Article

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