The solution structure of the pleckstrin homology domain of mouse Son-of-sevenless 1 (mSos1).
The solution structure of the pleckstrin 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 beta-strands and one alpha-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 alpha-helix, which interacts with the beta-sheet structure of the fundamental PH fold. Second, there is a long unstructured loop between beta3 and beta4. 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 beta1/beta2 loop and the N- and C-terminal parts of the long beta3/beta4 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 Cdelta1, and is clearly different from those of other PH domains.
Koshiba
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S
Cellular Signaling Laboratory, The Institute of Physical and Chemical Research (RIKEN), Wako, Saitama, Japan.
Kigawa
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T
Kim
J H
JH
Shirouzu
M
M
Bowtell
D
D
Yokoyama
S
S
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001798:Blood Proteins / Q000737:chemistry*; D020662:Guanine Nucleotide Exchange Factors; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D010750:Phosphoproteins; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012996:Solutions; D020663:ras Guanine Nucleotide Exchange Factors
D001798:Blood Proteins; D020662:Guanine Nucleotide Exchange Factors; D019269:Phosphatidylinositol 4,5-Diphosphate; D010750:Phosphoproteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D012996:Solutions; C039077:platelet protein P47; D020663:ras Guanine Nucleotide Exchange Factors; D015544:Inositol 1,4,5-Trisphosphate