Evolution of a new enzyme activity from the same motif fold

Abstract

The host cell recognition protein of the Escherichia coli bacteriophage HK620 is a large homotrimeric tailspike that cleaves the O18A1 type O antigen. The crystal structure of HK620 tailspike determined in the apo and substrate-bound form is reported by Barbirz et al. in this issue of Molecular Microbiology. Lacking detectable sequence similarity, the fold and overall organization of the HK620 tailspike are similar to those of the tailspikes of the related phages P22 and Sf6. The substrate-binding site is intrasubunit in P22 and HK620 tailspikes, but intersubunit in Sf6, demonstrating how phages can adapt the same protein fold to recognize different substrates.

Figure 1

A schematic showing the position of the active sites on the β-helices of three related tailspikes: P22, Sf6, and HK620 (Barbirz et al., 2008), (Müller et al., 2008; Steinbacher et al., 1996). A 20 Å-thick slice through the structure of the P22 tailspike in the region containing the active sites is shown. The slice is perpendicular to the threefold axis of the protein that is indicated with a black triangle. Three polypeptide chains are coloured red, green, and blue. The positions of the P22/HK620 (intrasubunit) and Sf6 (intersubunit) active sites are indicated with cyan and magenta hexagons, respectively.