Multiple
Pathways in Capsid Assembly
Posted on 2018-04-19 - 18:48
For
a three-dimensional structure to spontaneously self-assemble
from many identical components, the steps on the pathway must be kinetically
accessible. Many virus capsids are icosahedral and assembled from
hundreds of identical proteins, but how they navigate the assembly
process is poorly understood. Capsid assembly is thought to involve
stepwise addition of subunits to a growing capsid fragment. Coarse-grained
models suggest that the reaction occurs on a downhill energy landscape,
so intermediates are expected to be fleeting. In this work, charge
detection mass spectrometry (CDMS) has been used to track assembly
of the hepatitis B virus (HBV) capsid in real time. The icosahedral T = 4 capsid of HBV is assembled from 120 capsid protein
dimers. Our results indicate that there are multiple pathways for
assembly. Under conditions that favor a modest association energy
there is no accumulation of large intermediates, which indicates that
available pathways include ones on a downhill energy surface. Under
higher salt conditions, where subunit interactions are strengthened,
around half of the products of the initial assembly reaction have
masses close to the T = 4 capsid and the other half
are stalled intermediates which emerge abruptly at around 90 dimers,
indicating a bifurcation in the ensemble of assembly paths. When incubated
at room temperature, the 90-dimer intermediates accumulate dimers
and gradually shift to higher mass and merge with the capsid peak.
Though free subunits are present in solution, the stalled intermediates
indicate the presence of a local minima on the energy landscape. Some
intermediates may result from hole closure, where the growing capsid
distorts to close the hole due to the missing capsid proteins or from
a species where subsequent additions are particularly labile.
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Lutomski, Corinne
A.; Lyktey, Nicholas A.; Pierson, Elizabeth E.; Zhao, Zhongchao; Zlotnick, Adam; Jarrold, Martin F. (2018). Multiple
Pathways in Capsid Assembly. ACS Publications. Collection. https://doi.org/10.1021/jacs.8b01804
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AUTHORS (6)
CL
Corinne
A. Lutomski
NL
Nicholas A. Lyktey
EP
Elizabeth E. Pierson
ZZ
Zhongchao Zhao
AZ
Adam Zlotnick
MJ
Martin F. Jarrold