Structure of a viral procapsid with molecular scaffolding


The assembly of a macromolecular structure proceeds along an ordered morphogenetic pathway, and is accomplished by the switching of proteins between discrete conformations as they are added to the nascent assembly1,2,3. Scaffolding proteins often play a catalytic role in the assembly process1,2,4, rather like molecular chaperones5. Although macromolecular assembly processes are fundamental to all biological systems, they have been characterized most thoroughly in viral systems, such as the icosahedral Escherichia coli bacteriophage φX174 (refs 6, 7). The φX174 virion contains the proteins F, G, H and J7,8. During assembly, two scaffolding proteins B and D are required for the formation of a 108S, 360-Å-diameter procapsid from pentameric precursors containing the F, G and H proteins6,9. The procapsid contains 240 copies of protein D, forming an external scaffold, and 60 copies each of the internal scaffolding protein B, the capsid protein F, and the spike protein G9,10. Maturation involves packaging of DNA and J proteins and loss of protein B, producing a 132S intermediate6,7. Subsequent removal of the external scaffold yields the mature virion. Both the F and G proteins have the eight-stranded antiparallel β-sandwich motif8,11 common to many plant and animal viruses12,13. Here we describe the structure of a procapsid-like particle at 3.5-Å resolution, showing how the scaffolding proteins coordinate assembly of the virus by interactions with the F and G proteins, and showing that the F protein undergoes conformational changes during capsid maturation.

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Figure 1: Isosurface representation of a 10-Å resolution electron-density map of the whole closed procapsid particle, viewed down a 2-fold axis.
Figure 2: Cα backbone plot of the F protein in the closed procapsid (red).
Figure 3: Ribbon diagram29 showing the arrangement of the four D scaffolding proteins in one icosahedral asymmetric unit triangle, coloured as in Fig. 1a, viewed down a 2-fold axis.
Figure 4: Structural comparison of the D subunits.
Figure 5: Early steps in the assembly pathway of φX174.


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We thank the staff at the Cornell High Energy Synchrotron Source and the National Light Source staff at beam line X12 for providing the data collection facilities; W. F. Bean for help with computational work; and S. Wilder for help in the preparation of this manuscript. This study was supported by a National Science Foundation grant to M.G.R., an NIH grant to B.A.F., a Robert and Richard Rizzo Memorial Fund grant and an NIH grant to N.L.I., a Lucille P. Markey Foundation award to Purdue University, and a Purdue University reinvestment program grant. T.D. was supported by a European Molecular Biology Organization long-term postdoctoral fellowship for some of the time of this work.

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Dokland, T., McKenna, R., Ilag, L. et al. Structure of a viral procapsid with molecular scaffolding. Nature 389, 308–313 (1997).

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