High-affinity binding of a FYVE domain to phosphatidylinositol 3-phosphate requires intact phospholipid but not FYVE domain oligomerization

V. G. Sankaran, D. E. Klein, M. M. Sachdeva, M. A. Lemmon

Research output: Contribution to journalArticle

Abstract

FYVE domains are small zinc-finger-like domains found in many proteins that are involved in regulating membrane traffic and have been shown to bind specifically to phosphatidylinositol 3-phosphate (PtdIns-3-P). FYVE domains are thought to recruit PtdIns-3-P effectors to endosomal locations in vivo, where these effectors participate in controlling endosomal maturation and vacuolar protein sorting. We have compared the characteristics of PtdIns-3-P binding by the FYVE domain from Hrs-1 (the hepatocyte growth factor-regulated tyrosine kinase substrate) with those of specific phosphoinositide binding by Pleckstrin homology (PH) domains. Like certain PH domains (such as that from phospholipase C-δ1), the Hrs-1 FYVE domain specifically recognizes a single phosphoinositide. However, while phosphoinositide binding by highly specific PH domains is driven almost exclusively by interactions with the lipid headgroup, this is not true for the Hrs-1 FYVE domain. The phospholipase C-δ1 PH domain shows a 10-fold preference for binding isolated headgroup over its preferred lipid (phosphatidylinositol 4,5-bisphosphate) in a membrane, while the Hrs-1 FYVE domain greatly prefers (more than 50-fold) intact lipid in a bilayer over the isolated headgroup (inositol 1,3-bisphosphate). By contrast with reports for certain PH domains, we find that this preference for membrane binding over interaction with soluble lipid headgroups does not require FYVE domain oligomerization.

Original languageEnglish (US)
Pages (from-to)8581-8587
Number of pages7
JournalBiochemistry
Volume40
Issue number29
DOIs
StatePublished - Jul 24 2001
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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