Distinct specificity in the recognition of phosphoinositides by the pleckstrin homology domains of dynamin and Bruton's tyrosine kinase - PubMed (original) (raw)

. 1996 Nov 15;15(22):6241-50.

M J Bottomley, E Querfurth, M J Zvelebil, I Gout, R Scaife, R L Margolis, R Gigg, C I Smith, P C Driscoll, M D Waterfield, G Panayotou

Affiliations

Distinct specificity in the recognition of phosphoinositides by the pleckstrin homology domains of dynamin and Bruton's tyrosine kinase

K Salim et al. EMBO J. 1996.

Abstract

Pleckstrin homology (PH) domains may act as membrane localization modules through specific interactions with phosphoinositide phospholipids. These interactions could represent responses to second messengers, with scope for regulation by soluble inositol polyphosphates. A biosensor-based assay was used here to probe interactions between PH domains and unilamellar liposomes containing different phospholipids and to demonstrate specificity for distinct phosphoinositides. The dynamin PH domain specifically interacted with liposomes containing phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] and, more weakly, with liposomes containing phosphatidylinositol-4-phosphate [PI(4)P]. This correlates with phosphoinositide activation of the dynamin GTPase. The functional GTPase of a dynamin mutant lacking the PH domain, however, cannot be activated by PI(4,5)P2. The phosphoinositide-PH domain interaction can be abolished selectively by point mutations in the putative binding pocket predicted by molecular modelling and NMR spectroscopy. In contrast, the Bruton's tyrosine kinase (Btk)PH domain specifically bound liposomes containing phosphatidylinositol-3,4,5-trisphosphate [PI(3,4,5)P3]: an interaction requiring Arg28, a residue found to be mutated in some X-linked agammaglobulinaemia patients. A rational explanation for these different specificities is proposed through modelling of candidate binding pockets and is supported by NMR spectroscopy.

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References

    1. Cell. 1994 Oct 21;79(2):199-209 - PubMed
    1. Nature. 1994 Sep 8;371(6493):168-70 - PubMed
    1. Biochem Biophys Res Commun. 1994 Dec 30;205(3):1563-71 - PubMed
    1. J Biomol NMR. 1994 Nov;4(6):845-58 - PubMed
    1. Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):816-20 - PubMed

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