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Membrane Association of the PTEN Tumor Suppressor: Molecular Details of the Protein-Membrane Complex from SPR Binding Studies and Neutron Reflection



Siddharth Shenoy, Prabhanshu Shekhar, Frank Heinrich, Maria-Claire Daou, Arne Gericke, Alonzo H. Ross, Mathias Loesche


The structure and function of the PTEN phosphatase is investigated by studying its membrance affinity and localization on in-plane fluid, thermally disordered synthetic membrane models. The membrane association of the protein depends strongly on membrane composition, where phosphatidylserine (PS) and phosphoinositoldiphosphate (PI(4,5)P2) act pronouncedly synergetic in pulling the enzyme to the membrane surface. While the equilibrium dissociation constants for the binding of wild type (wt) PTEN to PS and PI(4,5)P2 were determined to be Kd^ 12 υM and 0.4 υM, respectively, Kd50 nM if both lipids are present. Membrane affinities depend critically on membrane fluidity, which suggests multiple binding sites on the protein for PI(4,5)P2. The PTEN mutations C124S and H93R show binding affinities which deviate strongly from those measured for the wt protein. Both mutants bind PS more strongly thant wt PTEN. While C124S PTEN has at least the same affinity to PI(4,5)P2 and an increased apparent affinity to PI(3,4,5)P3, due to its catalytic incapacitation, H93R PTEN shows a decreased affinity to PI(4,5)P2 and no synergy its binding with PS. Neutron reflection measurements show that the PTEN phosphatase "scoops" the membrane surface superficially (penetration less than} 5 A) but binds the membrane tightly with its major domains, a C2 domains and the phosphatase domain, as suggested by the crystal structure. The regulatory C-terminal tail is most likely displaced from the membrane and organized on the far side of the protein, 60 A away from the bilayer surface, in a rather compact structure.
Plos One


PTEN, membrane protein, surface plasmon resonance spectroscopy, neutron reflectometry, phosphate and tensin homologue deleted on chromosome 10


Shenoy, S. , Shekhar, P. , Heinrich, F. , Daou, M. , Gericke, A. , Ross, A. and Loesche, M. (2012), Membrane Association of the PTEN Tumor Suppressor: Molecular Details of the Protein-Membrane Complex from SPR Binding Studies and Neutron Reflection, Plos One, [online], (Accessed June 14, 2024)


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Created April 9, 2012, Updated October 12, 2021