Investigating the mechanical properties and flexibility of N-BAR domains in PICK1 by molecular dynamics simulations.

Abstract

Bin/Amphiphysin/Rvs167 (BAR) domain superfamily proteins are considered to be able to induce membrane curvature. PICK1 is a unique protein consisting of both a PDZ and a BAR domain that has been associated with many diseases. PICK1 can force membrane curvature during receptor-mediated endocytosis. In addition to understanding how the N-BAR domain can force membrane curvature, it is also of particular interest to understand the hidden connections between structural and mechanical properties of the PICK1 BAR dimers. In this paper, steered molecular dynamics is used to investigate the mechanical properties that are associated with structural changes of the PICK1 BAR domains. Our results suggest that helix kinks may not only help generate curvature of BAR domains but may also provide the extra flexibility necessary to initiate the binding between BAR domains and the membrane. Interestingly, we observe a complicated interaction network both within the BAR monomer and at the binding interface of the two BAR monomers that is key to maintain the mechanical properties of the BAR dimer. Because of such an interaction network, the PICK1 BAR dimer demonstrated different responses to external forces in opposite directions.