Structural transitions during the scaffolding-driven assembly of a viral capsid

Athanasios Ignatiou,Maya Topf,Mehdi El Sadek Fadel,Paulo Tavares,Thorsten Mielke,Sandrine Brasilès,Jörg Bürger,Elena V Orlova

doi:10.1038/s41467-019-12790-6

Abstract

Assembly of tailed bacteriophages and herpesviruses starts with formation of procapsids (virion precursors without DNA). Scaffolding proteins (SP) drive assembly by chaperoning the major capsid protein (MCP) to build an icosahedral lattice. Here we report near-atomic resolution cryo-EM structures of the bacteriophage SPP1 procapsid, the intermediate expanded procapsid with partially released SPs, and the mature capsid with DNA. In the intermediate state, SPs are bound only to MCP pentons and to adjacent subunits from hexons. SP departure results in the expanded state associated with unfolding of the MCP N-terminus and straightening of E-loops. The newly formed extensive inter-capsomere bonding appears to compensate for release of SPs that clasp MCP capsomeres together. Subsequent DNA packaging instigates bending of MCP A domain loops outwards, closing the hexons central opening and creating the capsid auxiliary protein binding interface. These findings provide a molecular basis for the sequential structural rearrangements during viral capsid maturation.

Highlights

Of tailed bacteriophages and herpesviruses starts with formation of procapsids
Structures of Superposition of the gp13 (SPP1) procapsids and capsids purified from Bacillus subtilis infected cells were determined by Cryo-electron microscopy (cryo-EM)
We found that the preparations of SPP1 procapsids, which are biologically active for DNA packaging[19], contain two major populations

Summary

Introduction

Of tailed bacteriophages and herpesviruses starts with formation of procapsids (virion precursors without DNA). We report near-atomic resolution cryo-EM structures of the bacteriophage SPP1 procapsid, the intermediate expanded procapsid with partially released SPs, and the mature capsid with DNA. Subsequent DNA packaging instigates bending of MCP A domain loops outwards, closing the hexons central opening and creating the capsid auxiliary protein binding interface These findings provide a molecular basis for the sequential structural rearrangements during viral capsid maturation. Maturation of the procapsid to the DNA-filled capsid state requires SP release and DNA packaging (Fig. 1a) These processes are accompanied by dramatic overall rearrangements of the MCP lattice that increases in size and becomes thinner. We report near-atomic models built into cryo-EM structures of procapsid I, intermediate procapsid II which has partially released the SP, and the mature DNA-filled capsid from bacteriophage SPP1. The structures obtained reveal distinct steps of the MCP conformational transitions during capsid maturation that correlate with release of the SP and with DNA packaging that were uncoupled in this study

Methods

Results

Conclusion