Structure of apo-phosphatidylinositol transfer protein α provides insight into membrane association

Arie Schouten, Bogos Agianian, Jan Westerman, Jan Kroon, Karel W A Wirtz, Piet Gros

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Phosphatidylinositol transfer protein α (PITPα) is a ubiquitous and highly conserved protein in multicellular eukaryotes that catalyzes the exchange of phospholipids between membranes in vitro and participates in cellular phospholipid metabolism, signal transduction and vesicular trafficking in vivo. Here we report the three-dimensional crystal structure of a phospholipid-free mouse PITPα at 2.0 Å resolution. The structure reveals an open conformation characterized by a channel running through the protein. The channel is created by opening the phospholipid-binding cavity on one side by displacement of the C-terminal region and a hydrophobic lipid exchange loop, and on the other side by flattening of the central β-sheet. The relaxed conformation is stabilized at the proposed membrane association site by hydrophobic interactions with a crystallographically related molecule, creating an intimate dimer. The observed open conformer is consistent with a membrane-bound state of PITP and suggests a mechanism for membrane anchoring and the presentation of phosphatidylinositol to kinases and phospholipases after its extraction from the membrane. Coordinates have been deposited in the Protein Data Bank (accession No. 1KCM).

Original languageEnglish (US)
Pages (from-to)2117-2121
Number of pages5
JournalEMBO Journal
Volume21
Issue number9
DOIs
StatePublished - May 1 2002
Externally publishedYes

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Phospholipid Transfer Proteins
Association reactions
Phospholipids
Membranes
Conformations
Signal transduction
Proteins
Phospholipases
Phosphatidylinositols
Eukaryota
Hydrophobic and Hydrophilic Interactions
Metabolism
Dimers
Signal Transduction
Phosphotransferases
Crystal structure
Databases
Lipids
Molecules

Keywords

  • Membrane association
  • Phospholipid-binding protein
  • PITP

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Structure of apo-phosphatidylinositol transfer protein α provides insight into membrane association. / Schouten, Arie; Agianian, Bogos; Westerman, Jan; Kroon, Jan; Wirtz, Karel W A; Gros, Piet.

In: EMBO Journal, Vol. 21, No. 9, 01.05.2002, p. 2117-2121.

Research output: Contribution to journalArticle

Schouten, Arie ; Agianian, Bogos ; Westerman, Jan ; Kroon, Jan ; Wirtz, Karel W A ; Gros, Piet. / Structure of apo-phosphatidylinositol transfer protein α provides insight into membrane association. In: EMBO Journal. 2002 ; Vol. 21, No. 9. pp. 2117-2121.
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