Structure of the iSH2 domain of human phosphatidylinositol 3-kinase p85Β subunit reveals conformational plasticity in the interhelical turn region

Curtis Schauder, Li Chung Ma, Robert M. Krug, Gaetano T. Montelione, Rongjin Guan

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageAmerican English
Pages (from-to)1567-1571
Number of pages5
JournalActa Crystallographica Section F: Structural Biology and Crystallization Communications
Issue number12
StatePublished - Dec 2010

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Genetics
  • Condensed Matter Physics


  • iSH2 domain
  • influenza virus NS1 protein binding
  • p85Β unit
  • phosphatidylinositol 3-kinases

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