Pleckstrin homology domains bind to phosphatidylinositol-4,5-bisphosphate
Harlan, John E.
Hajduk, Philip J.
Yoon, Ho Sup
Fesik, Stephen W.
Date of Issue1994
School of Biological Sciences
Abbott Laboratories, Pharmaceutical Discovery Division, NMR Research, D-47G, AP9, Abbott Park, Illinois 60064, USA
THE pleckstrin homology (PH) domain is a new protein module of around 100 amino acids found in several proteins involved in signal transduction1–5. Although its specific function has yet to be elucidated, the carboxy-terminal regions of many βγ domains bind to the py subunits of G proteins6,7. On the basis of structural similarities between PH domains and lipid-binding proteins, we have proposed that PH domains may be binding to lipophilic molecules8. Indeed, many of the proteins that contain this domain associate with phospholipid membranes6,9,10, and disruption of this domain can interfere with membrane association6,11. Here we report that PH domains bind to phosphatidylinositol-4,5-bisphosphate and show that the lipid-binding site is located at the lip of the β-barrel. This suggests that PH domains may be important for membrane localization of proteins through interactions with phosphatidylinositol-4,5-bisphosphate.
© 1994 Nature Publishing Group. This is the author created version of a work that has been peer reviewed and accepted for publication by Nature, Nature Publishing Group. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [DOI: http://dx.doi.org/10.1038/371168a0 ].