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Phage procapsids - how do they work?

Harry Caufield

Been thinking about bacteriophage capsid assembly a bit today. For all we know about phages, and other double-stranded DNA viruses for that matter, a few steps in their assembly remain difficult to explain.

Some of my notes on a lecture from 2011. "Escape" probably isn't the right word, and that last word should be "scaffold", but you get the idea.

Some of my notes on a lecture from 2011. "Escape" probably isn't the right word, and that last word should be "scaffold", but you get the idea.

Here's one such question: when phage scaffold proteins undergo proteolysis during capsid maturation, what happens to all the resulting peptides? As far as I know, the scaffold has to get processed at some point during phage particle maturation (see Medina et al. 2010, cited below, for the lambda example) but that capsid is a cramped environment without many exit routes. Do the scaffold bits just leak out through the capsid somewhere? (Perhaps more importantly, what about situations requiring a distinct prohead protease? Where does that enzyme go once it's done all its protein processing?)

There are some recent modeling-based studies of phage capsid maturation (e.g., Jiang et al. 2015) but they still don't seem to account for proteolysis, just conformation at particular maturation stages.

Has someone already solved this mystery? Is it really a mystery in the first place, or am I just missing something?

* Medina, Elizabeth, Doug Wieczorek, Eva Margarita Medina, Qin Yang, Michael Feiss, and Carlos Enrique Catalano. 2010. “Assembly and Maturation of the Bacteriophage Lambda Procapsid: GpC Is the Viral Protease.” Journal of Molecular Biology 401 (5). Elsevier Ltd: 813–30. doi:10.1016/j.jmb.2010.06.060.

* Jiang, Jiajian, Jing Yang, Yuriy V Sereda, and Peter J Ortoleva. 2015. “Early Stage P22 Viral Capsid Self-Assembly Mediated by Scaffolding Protein: Atom-Resolved Model and Molecular Dynamics Simulation.” The Journal of Physical Chemistry. B 119 (16). American Chemical Society: 5156–62. doi:10.1021/acs.jpcb.5b00303.