Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery: Bridging Experiments and Computations - September 10-14, 2014, Istanbul, Turkey

Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Poster Session II

95-POS Board 48 Molecular Mechanism Underlying Recruitment of a Lipid-Anchored Protein Lipi Thukral 1 , Durba Sengupta 2 , Nikhil Agrawal 1 , Amrita Ramkumar 1 , Divya Murthy 1 , Rajesh S. Gokhale 1 1 CSIR-Institute of Genomics and Integrative Biology, New Delhi, India, 2 CSIR-National Chemical Laboratory (NCL), Pune, India Eukaryotic cells possess potential regulatory mechanisms to mediate many of its protein- membrane interactions in form of lipid-modified proteins. These highly specialized proteins have a unique architecture of a lipid anchor that enables them to peripherally dock onto negatively charged membrane surfaces in lipid-bound conformation. However, molecular events underlying this process of attachment to membrane is poorly understood. In this study, we investigate membrane recruitment of microtubule-associated protein light chain 3 (LC3) modified with phosphatidylethanolamine (PE) using multiple independent microsecond time- scale coarse-grain simulations. Spontaneous insertion events of lipid anchor were observed in multiple simulations, which allowed us to dissect the molecular mechanism of insertion with high statistical reliability. Positively charged residues in this helix especially ASN59, LYS65, and ARG68 ensures a stable and efficient delivery of PE chain into membrane. In addition, generation LC3 mutants showed distinct difference in puncta formation and localization when expressed in vivo, further substantiating the hypothesis. Thus, our study of active insertion of PE chain provides future avenues to investigate detailed regulatory aspects of this using biological process.

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