Waltmann Curt, Asor Roi, Raviv Uri, Olvera de la Cruz Monica
Department of Materials Science and Engineering, Northwestern University, Evanston, Illinois 60208, United States.
Institute of Chemistry, The Hebrew University of Jerusalem, Edmond J Safra Campus, Givat Ram, Jerusalem, 9190401, Israel.
ACS Nano. 2020 Apr 28;14(4):4430-4443. doi: 10.1021/acsnano.9b10004. Epub 2020 Apr 2.
Understanding viral assembly pathways is of critical importance to biology, medicine, and nanotechology. Here, we study the assembly path of a system with various structures, the simian vacuolating virus 40 (SV40) polymorphs. We simulate the templated assembly process of VP1 pentamers, which are the constituents of SV40, into icosahedal shells made of = 12 pentamers ( = 1). The simulations include connections formed between pentamers by C-terminal flexible lateral units, termed here "C-terminal ligands", which are shown to control assembly behavior and shell dynamics. The model also incorporates electrostatic attractions between the N-terminal peptide strands (ligands) and the negatively charged cargo, allowing for agreement with experiments of RNA templated assembly at various pH and ionic conditions. During viral assembly, pentamers bound to any template increase its effective size due to the length and flexibility of the C-terminal ligands, which can connect to other VP1 pentamers and recruit them to a partially completed capsid. All closed shells formed other than the = 1 feature the ability to dynamically rearrange and are thus termed "pseudo-closed". The = 13 shell can even spontaneously "self-correct" by losing a pentamer and become a = 1 capsid when the template size fluctuates. Bound pentamers recruiting additional pentamers to dynamically rearranging capsids allow closed shells to continue growing the pseudo-closed growth mechanism, for which experimental evidence already exists. Overall, we show that the C-terminal ligands control the dynamic assembly paths of SV40 polymorphs.
了解病毒组装途径对生物学、医学和纳米技术至关重要。在此，我们研究了具有多种结构的系统——猴空泡病毒40（SV40）多晶型物的组装途径。我们模拟了VP1五聚体（SV40的组成成分）组装成由12个五聚体（T = 1）构成的二十面体外壳的模板组装过程。模拟包括由C端柔性侧向单元（在此称为“C端配体”）在五聚体之间形成的连接，这些连接被证明可控制组装行为和外壳动力学。该模型还纳入了N端肽链（配体）与带负电荷的货物之间的静电吸引力，从而能够与在各种pH和离子条件下的RNA模板组装实验结果相符。在病毒组装过程中，由于C端配体的长度和柔性，与任何模板结合的五聚体会增加其有效尺寸，C端配体可连接到其他VP1五聚体并将它们招募到部分完成的衣壳中。除了T = 1的情况外，形成的所有封闭外壳都具有动态重排的能力，因此被称为“假封闭”。当模板尺寸波动时，T = 13的外壳甚至可以通过失去一个五聚体而自发“自我校正”，变成T = 1的衣壳。结合的五聚体将额外的五聚体招募到动态重排的衣壳中，使得封闭外壳能够通过假封闭生长机制继续生长，对此已有实验证据。总体而言，我们表明C端配体控制着SV40多晶型物的动态组装途径。
