RT Journal Article
SR Electronic
T1 “Coarse-grained simulation reveals key features of HIV-1 capsid self-assembly”
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 040741
DO 10.1101/040741
A1 John M. A. Grime
A1 James F. Dama
A1 Barbie K. Ganser-Pornillos
A1 Cora L. Woodward
A1 Grant J. Jensen
A1 Mark J. Yeager
A1 Gregory A. Voth
YR 2016
UL http://biorxiv.org/content/early/2016/02/23/040741.abstract
AB The maturation of HIV-1 viral particles is essential for viral infectivity. During maturation, many copies of the capsid protein (CA) self-assemble into a capsid shell to enclose the viral RNA. The mechanistic details of the initiation and early stages of capsid assembly remain to be delineated. We present coarse-grained simulations of capsid assembly under various conditions, considering not only capsid lattice self-assembly but also the potential disassembly of capsid upon delivery to the cytoplasm of a target cell. The effects of CA concentration, molecular crowding, and the conformational variability of CA are described, with results indicating that capsid nucleation and growth is a multi-stage process requiring well-defined metastable intermediates. Generation of the mature capsid lattice is sensitive to local conditions, with relatively subtle changes in CA concentration and molecular crowding influencing self-assembly and the ensemble of structural morphologies.