Computational Study of the Inter-Domain Stabilization of Tandem Green Fluorescent Substrate Proteins During Proteasomal Degradation Initiated From Internal Sites

Main Article Content

Lillian Ganote George Stan


By Lillian Ganote, Chemistry

Advisor: George Stan

Presentation ID: AM_D01

Abstract: The 26S proteasome is an ATP-dependent degradation machine that maintains cell viability by unfolding and degradation of ubiqutinated proteins in eukaryotes. These actions are mediated by a ring-shaped AAA-ATPase heterohexamer (Rpt1-6) motor that unfold substrate protein (SP) and thread them through a narrow central pore. In this study, we use a coarse-grained model of AAA+ ATPase motor of 26S proteasome and perform langevin dynamics simulation of mechanical pulling of GFP and tandem GFP (N-GFP-linker-GFP-C) through the center pore of AAA+ ATPase motor. We compare and contrast mechanical unfolding of GFP in the bulk and mediated by the proteasome. Our results reveal an inter-domain stabilization of GFP dimer and increased mechanical stability of GFP dimer compare to the monomer. They also show an asymmetry in complete protection and complete unfolding of N-GFP and GFP-C so that N-GFP unfolding prior to GFP-C is the major pathway. We attribute these two distinct unfolding mechanisms to the diverged orientations of tandem domains.

Article Details

AM Poster Session -- Great Hall -- D: New Frontiers