Terminase Subunits from the Pseudomonas-Phage E217

Viral Small Terminase: A Divergent Structural Framework for a Conserved Biological Function

“…During all three steps described above, TerL undergoes major conformational rearrangements. It is typically monomeric in solution [ 16 , 25 , 26 , 27 , 28 ] but oligomerizes into a pentamer bound to the portal dodecamer [ 20 , 22 ], generating a symmetry mismatch with the portal vertex [ 29 , 30 ]. A high-resolution localized reconstruction of phi29 TerL bound to an immature phi29 capsid [ 31 ] found that the TerL oligomer adopts a helical conformation lacking rotational symmetry.…”

“…Similarly, TerS inhibited packaging in a defined in vitro packaging system carried out in the presence of purified T4 [ 39 , 40 , 41 ] or SPP1 [ 42 ] components. Along the same lines, a single-molecule packaging assay for T4 was strongly inhibited by an excess of TerS [ 2 , 43 ] and, similarly, the overexpression of TerS in a complementation assay reduces phage E217 infectivity [ 28 ]. Thus, TerS is an essential viral subunit whose function is not easily recapitulated in vitro, suggesting a strictly concentration-dependent function and short kinetic window of action.…”

“…However, the physical proximity of the TerS and TerL genes is not a universal feature. Lokareddy et al found the TerS gene of phage E217 is ~58 kbs away from the TerL gene, on the opposite side of the genome [ 28 ].…”

“…The structure of several TerSs from bacteriophage and HSV-1 has been investigated using biophysical methods, providing a useful framework for understanding their assembly and activity. Three-dimensional structures have been obtained for TerS from bacteriophages that infect Escherichia coli (i.e., λ [ 58 ], T4-like 44RR [ 59 ], HK97 [ 60 ]), Shigella flexneri (i.e., Sf6 [ 61 , 62 ]), Salmonella enterica (i.e., P22 [ 63 , 64 , 65 , 66 ]), Bacillus subtilis (i.e., SF6, SPP1 [ 67 ]), Pseudomonas aeruginosa (i.e., PaP3 [ 68 ], NV1 [ 68 ], E217 [ 28 ]), and Thermus thermophilus (i.e., G20c [ 69 ], P74–26 [ 70 ]) ( Table 1 ). All atomic structures of phage TerSs reported between 2002 and 2019 were solved using X-ray methods or used NMR for a fragment of phage λ TerS [ 58 ].…”

“…All atomic structures of phage TerSs reported between 2002 and 2019 were solved using X-ray methods or used NMR for a fragment of phage λ TerS [ 58 ]. Since the advent of the cryo-EM revolution [ 71 ], single-particle reconstructions were reported for phage P74-26 [ 70 ] and E217 [ 28 ] TerS, as well as HSV-1 pUL28 (TerS), determined in complex with pUL15 (TerL) and pUL33 [ 72 ]. As pointed out above, there is no structural similarity or evolutionary conservation between phages and herpesviruses TerSs, which are different proteins of similar function (described in Section 7 ).…”