148
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.
