Structural basis for phosphoinositide substrate recognition, catalysis, and membrane interactions in human inositol polyphosphate 5-phosphatases.

نویسندگان

  • Lionel Trésaugues
  • Camilla Silvander
  • Susanne Flodin
  • Martin Welin
  • Tomas Nyman
  • Susanne Gräslund
  • Martin Hammarström
  • Helena Berglund
  • Pär Nordlund
چکیده

SHIP2, OCRL, and INPP5B belong to inositol polyphosphate 5-phophatase subfamilies involved in insulin regulation and Lowes syndrome. The structural basis for membrane recognition, substrate specificity, and regulation of inositol polyphosphate 5-phophatases is still poorly understood. We determined the crystal structures of human SHIP2, OCRL, and INPP5B, the latter in complex with phosphoinositide substrate analogs, which revealed a membrane interaction patch likely to assist in sequestering substrates from the lipid bilayer. Residues recognizing the 1-phosphate of the substrates are highly conserved among human family members, suggesting similar substrate binding modes. However, 3- and 4-phosphate recognition varies and determines individual substrate specificity profiles. The high conservation of the environment of the scissile 5-phosphate suggests a common reaction geometry for all members of the human 5-phosphatase family.

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عنوان ژورنال:
  • Structure

دوره 22 5  شماره 

صفحات  -

تاریخ انتشار 2014