Phosphatidylinositol 3-phosphate induces the membrane penetration of the FYVE domains of Vps27p and Hrs

Robert Stahelin, Fei Long, Karthikeyan Diraviyam, Karol S. Bruzik, Diana Murray, Wonhwa Cho

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

The FYVE domain mediates the recruitment of proteins involved in membrane trafficking and cell signaling to phosphatidylinositol 3-phosphate (PtdIns(3)P)-containing membranes. To elucidate the mechanism by which the FYVE domain interacts with PtdIns(3)P-containing membranes, we measured the membrane binding of the FYVE domains of yeast Vps27p and Drosophila hepatocyte growth factor-regulated tyrosine kinase substrate and their mutants by surface plasmon resonance and monolayer penetration analyses. These measurements as well as electrostatic potential calculation show that PtdIns(3)P specifically induces the membrane penetration of the FYVE domains and increases their membrane residence time by decreasing the positive charge surrounding the hydrophobic tip of the domain and causing local conformational changes. Mutations of hydrophobic residues located close to the PtdIns(3)P-binding pocket or an Arg residue directly involved in PtAIns(3)P binding abrogated the penetration of the FYVE domains into the monolayer, the packing density of which is comparable with that of biological membranes and large unilamellar vesicles. Based on these results, we propose a mechanism of the membrane binding of the FYVE domain in which the domain first binds to the PtdIns(3)P-containing membrane by specific PtdIns(3)P binding and nonspecific electrostatic interactions, which is then followed by the PtAIns(3)P-induced partial membrane penetration of the domain.

Original languageEnglish (US)
Pages (from-to)26379-26388
Number of pages10
JournalJournal of Biological Chemistry
Volume277
Issue number29
DOIs
StatePublished - Jul 19 2002
Externally publishedYes

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Membranes
Static Electricity
Monolayers
Cell signaling
Biological membranes
phosphatidylinositol 3-phosphate
Unilamellar Liposomes
Surface Plasmon Resonance
Surface plasmon resonance
Coulomb interactions
Yeast
Drosophila
Electrostatics
Yeasts
Cell Membrane
Mutation
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Phosphatidylinositol 3-phosphate induces the membrane penetration of the FYVE domains of Vps27p and Hrs. / Stahelin, Robert; Long, Fei; Diraviyam, Karthikeyan; Bruzik, Karol S.; Murray, Diana; Cho, Wonhwa.

In: Journal of Biological Chemistry, Vol. 277, No. 29, 19.07.2002, p. 26379-26388.

Research output: Contribution to journalArticle

Stahelin, Robert ; Long, Fei ; Diraviyam, Karthikeyan ; Bruzik, Karol S. ; Murray, Diana ; Cho, Wonhwa. / Phosphatidylinositol 3-phosphate induces the membrane penetration of the FYVE domains of Vps27p and Hrs. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 29. pp. 26379-26388.
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