The molecular basis of the differential subcellular localization of FYVE domains

Nichole R. Blatner, Robert V. Stahelin, Karthikeyan Diraviyam, Phillip T. Hawkins, Wanjin Hong, Diana Murray, Wonhwa Cho

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

This study systematically analyzed the structural and mechanistic basis of the regulation of subcellular membrane targeting using FYVE domains as a model. FYVE domains, which mediate the recruitment of signaling and membrane-trafficking proteins to phosphatidylinositol 3-phosphate-containing endosomes, exhibit distinct subcellular localization despite minor structural variations within the family. Biophysical measurements, cellular imaging, and computational analysis of various FYVE domains showed that the introduction of a single cationic residue and a hydrophobic loop into the membrane binding region of the FYVE domains dramatically enhanced their membrane interactions. The results indicated that there is a threshold affinity for endosomal localization and that endosomal targeting of FYVE domains is sensitive to small changes in membrane affinity about this threshold. Collectively these studies provide new insight into how subcellular localization of FYVE domains and other membrane targeting domains can be regulated by minimal structural and environmental changes.

Original languageEnglish (US)
Pages (from-to)53818-53827
Number of pages10
JournalJournal of Biological Chemistry
Volume279
Issue number51
DOIs
StatePublished - Dec 17 2004
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Blatner, N. R., Stahelin, R. V., Diraviyam, K., Hawkins, P. T., Hong, W., Murray, D., & Cho, W. (2004). The molecular basis of the differential subcellular localization of FYVE domains. Journal of Biological Chemistry, 279(51), 53818-53827. https://doi.org/10.1074/jbc.M408408200