The solution structure of the pleckstrin homology domain of mouse Son-of-sevenless 1 (mSos1)

Seizo Koshiba, Takanori Kigawa, Jae Hoon Kim, Mikako Shirouzu, David Bowtell, Shigeyuki Yokoyama

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)

Abstract

The solution structure of the plecktrin homology (PH) domain of mouse Son-of-sevenless 1 (mSos1), a guanine nucleotide exchange factor for Ras, was determined by multidimensional NMR spectroscopy. The structure of the mSos1 PH domain involves the fundamental PH fold, consisting of seven β-strands and one α-helix at the C terminus, as determined for the PH domains of other proteins. By contrast, the mSos1 PH domain showed two major characteristic features. First, the N-terminal region, whose amino acid sequence is highly conserved among Sos proteins, was found to form an α-helix, which interacts with the β-sheet structure of the fundamental PH fold. Second, there is a long unstructured loop between β3 and β4. Furthermore, the mSos1 PH domain was found to bind phosphatidylinositol-4,5-bisphosphate by a centrifugation assay. The addition of inositol-1,4,5-trisphosphate to the mSos1 PH domain induced backbone amide chemical shift changes mainly in the β1/β2 loop and the N- and C-terminal parts of the long β3/β4 loop. This inositol-1,4,5-trisphosphate-binding mode of the mSos1 PH domain is somewhat similar to those of the PH domains of pleckstrin and phospholipase Cδ1, and is clearly different from those of other PH domains.

Original languageEnglish
Pages (from-to)579-591
Number of pages13
JournalJournal of Molecular Biology
Volume269
Issue number4
DOIs
Publication statusPublished - 1997 Jun 20

Keywords

  • Inositol-1,4,5-trisphosphate
  • NMR
  • PH domain
  • Signal transduction
  • Solution structure

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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