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Structure of apo‐phosphatidylinositol transfer protein α provides insight into membrane association
Author(s) -
Schouten Arie,
Agianian Bogos,
Westerman Jan,
Kroon Jan,
Wirtz Karel W.A.,
Gros Piet
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/21.9.2117
Subject(s) - biology , phosphatidylinositol , phospholipid , membrane , biophysics , microbiology and biotechnology , protein structure , biochemistry , signal transduction
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 ).