Work

Two cooperative lipid binding sites within the pleckstrin homology domain are necessary for AKT binding and stabilization to the plasma membrane

Year: 2024

Type: article

Abstract: phase coexistence). We have applied molecular dynamic simulations and molecular and cell biology approaches, and demonstrate that AKT recruitment to the membrane requires a second binding site in the AKT pleckstrin homology (PH) domain that acts cooperatively with the known canonical binding site. Given the precision with which we have identified the protein-lipid interactions, the study offers new directions for AKT-targeted therapy and for testing small molecules to target these specific amino acid-PIP molecular bonds.

Source: Structure

DOI: 10.1016/j.str.2024.10.020

Authors: Chrysa Soteriou, Mengfan Xu, Simon D. Connell, Arwen I.I. Tyler, Antreas C. Kalli, James L. Thorne

Institution: University of Leeds

Language: English

Topic: PI3K/AKT/mTOR signaling in cancer

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $9,350

Funders: Wellcome Trust, University of Leeds