| Autor: |
Thomas N; Department of Mechanical Engineering, University of Houston, Houston, TX, 77204, USA. ashutosh@uh.edu., Combs W; Department of Mechanical Engineering, University of Houston, Houston, TX, 77204, USA. ashutosh@uh.edu., Mandadapu KK; Department of Chemical & Biomolecular Engineering, University of California, Berkeley, CA 94720, USA.; Chemical Sciences Division, Lawrence Berkeley National Laboratory, CA 94720, USA., Agrawal A; Department of Mechanical Engineering, University of Houston, Houston, TX, 77204, USA. ashutosh@uh.edu. |
| Abstrakt: |
Phosphatidic acid (PA) is an anionic lipid that preferentially interacts with proteins in a diverse set of cellular processes such as transport, apoptosis, and neurotransmission. One such interaction is that of the PA lipids with the proteins of voltage-sensitive ion channels. In comparison to several other similarly charged anionic lipids, PA lipids exhibit much stronger interactions. Intrigued and motivated by this finding, we sought out to gain deeper understanding into the electrostatic interactions of anionic lipids with charged proteins. Using the voltage sensor domain (VSD) of the KvAP channel as a model system, we performed long-timescale atomistic simulations to analyze the interactions of POPA, POPG, and POPI lipids with arginines (ARGs). Our simulations reveal two mechanisms. First, POPA is able to interact not only with surface ARGs but is able to snorkel and interact with a buried arginine. POPG and POPI lipids on the other hand show weak interactions even with both the surface and buried ARGs. Second, deprotonated POPA with -2 charge is able to break the salt-bridge connection between VSD protein segments and establish its own electrostatic bond with the ARG. Based on these findings, we propose a headgroup size hypothesis for preferential solvation of proteins by charged lipids. These findings may be valuable in understanding how PA lipids could be modulating kinematics of transmembrane proteins in cellular membranes. |
