The papillomavirus major capsid protein L1

Abstract

The elegant icosahedral surface of the papillomavirus virion is formed by a single protein called L1. Recombinant L1 proteins can spontaneously self-assemble into a highly immunogenic structure that closely mimics the natural surface of native papillomavirus virions. This has served as the basis for two highly successful vaccines against cancer-causing human papillomaviruses (HPVs). During the viral life cycle, the capsid must undergo a variety of conformational changes, allowing key functions including the encapsidation of the ~8 kb viral genomic DNA, maturation into a more stable state to survive transit between hosts, mediating attachment to new host cells, and finally releasing the viral DNA into the newly infected host cell. This brief review focuses on conserved sequence and structural features that underlie the functions of this remarkable protein.

Keywords: HPV; HPV16; L2; Maturation; Papillomaviridae; Virion.

Figure 1

Cryo-EM reconstruction of an HPV16 pseudovirion calculated at 18Å resolution, as described in (Buck and Trus, 2012). The figure shows a view down the axis of a capsomer at the icosahedral vertex.

Figure 2

Structure of an L1 capsomer. Images were drawn with PyMOL software <www.pymol.org> using the atomic coordinates of BPV1 L1 (Wolf et al., 2010). Each L1 chain was assigned a distinct color. The left panel shows a top view of a non-vertex capsomer, revealing the interdigitation of L1 loops on the surface of the capsomer knob. The right panel shows a side view of the capsomer in which the core beta jellyroll fold of L1 is visible. Conserved cysteines involved in inter-capsomeric disulfide bonds are highlighted as yellow spheres.