TY - JOUR
T1 - Should Virus Capsids Assemble Perfectly? Theory and Observation of Defects
AU - Spiriti, Justin
AU - Conway, James F.
AU - Zuckerman, Daniel M.
N1 - Publisher Copyright:
© 2020 Biophysical Society
PY - 2020/11/3
Y1 - 2020/11/3
N2 - Although published structural models of viral capsids generally exhibit a high degree of regularity or symmetry, structural defects might be expected because of the fluctuating environment in which capsids assemble and the requirement of some capsids for disassembly before genome delivery. Defective structures are observed in computer simulations, and are evident in single-particle cryoelectron microscopy studies. Here, we quantify the conditions under which defects might be expected, using a statistical mechanics model allowing for ideal, defective, and vacant sites. The model displays a threshold in affinity parameters below which there is an appreciable population of defective capsids. Even when defective sites are not allowed, there is generally some population of vacancies. Analysis of single particles in cryoelectron microscopy micrographs yields a confirmatory ≳15% of defective particles. Our findings suggest structural heterogeneity in virus capsids may be under-appreciated, and also points to a nontraditional strategy for assembly inhibition.
AB - Although published structural models of viral capsids generally exhibit a high degree of regularity or symmetry, structural defects might be expected because of the fluctuating environment in which capsids assemble and the requirement of some capsids for disassembly before genome delivery. Defective structures are observed in computer simulations, and are evident in single-particle cryoelectron microscopy studies. Here, we quantify the conditions under which defects might be expected, using a statistical mechanics model allowing for ideal, defective, and vacant sites. The model displays a threshold in affinity parameters below which there is an appreciable population of defective capsids. Even when defective sites are not allowed, there is generally some population of vacancies. Analysis of single particles in cryoelectron microscopy micrographs yields a confirmatory ≳15% of defective particles. Our findings suggest structural heterogeneity in virus capsids may be under-appreciated, and also points to a nontraditional strategy for assembly inhibition.
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U2 - 10.1016/j.bpj.2020.09.021
DO - 10.1016/j.bpj.2020.09.021
M3 - Article
C2 - 33113349
AN - SCOPUS:85094560814
SN - 0006-3495
VL - 119
SP - 1781
EP - 1790
JO - Biophysical Journal
JF - Biophysical Journal
IS - 9
ER -