Cookies

We use cookies to ensure that we give you the best experience on our website. You can change your cookie settings at any time. Otherwise, we'll assume you're OK to continue.

Durham University

Department of Biosciences

Academic Staff

Publication details for Prof A Walmsley

Baillie, G., Huston, E., Scotland, G., Warwicker, J., Hodgkin, M.N., Gall, I., Currie, R., Walmsley, A., Wakelam, M.J.O. & Houslay, M.D. (2002). TAPAS-1, a novel microdomain that allows rapid, Ca2+-dependent membrane association with selectivity for interaction with phosphatidic acid. Journal of Biological Chemistry 277(29): 28298-28309.

Author(s) from Durham

Abstract

Here we identify an 11-residue helical module in the unique N-terminal region of the cyclic AMP-specific phosphodiesterase PDE4A1 that determines association with phospholipid bilayers and shows a profound selectivity for interaction with phosphatidic acid (PA). This module contains a core bilayer insertion unit that is formed by two tryptophan residues, Trp19 and Trp20, whose orientation is optimized for bilayer insertion by the Leu16:Val17 pairing. Ca2+, at submicromolar levels, interacts with Asp21 in this module and serves to gate bilayer insertion, which is completed within 10 ms. Selectivity for interaction with PA is suggested to be achieved primarily through the formation of a charge network of the form (Asp21−:Ca2+:PA2−:Lys24+) with overall neutrality at the bilayer surface. This novel phospholipid-binding domain, which we call TAPAS-1 (tryptophan anchoring phosphatidicacid selective-binding domain 1), is here identified as being responsible for membrane association of the PDE4A1 cAMP-specific phosphodiesterase. TAPAS-1 may not only serve as a paradigm for other PA-binding domains but also aid in detecting related phospholipid-binding domains and in generating simple chimeras for conferring membrane association and intracellular targeting on defined proteins.