Phages have adapted the same protein fold to fulfill multiple functions in virion assembly

Abstract

Evolutionary relationships may exist among very diverse groups of proteins even though they perform different functions and display little sequence similarity. The tailed bacteriophages present a uniquely amenable system for identifying such groups because of their huge diversity yet conserved genome structures. In this work, we used structural, functional, and genomic context comparisons to conclude that the head–tail connector protein and tail tube protein of bacteriophage λ diverged from a common ancestral protein. Further comparisons of tertiary and quaternary structures indicate that the baseplate hub and tail terminator proteins of bacteriophage may also be part of this same family. We propose that all of these proteins evolved from a single ancestral tail tube protein fold, and that gene duplication followed by differentiation led to the specialized roles of these proteins seen in bacteriophages today. Although this type of evolutionary mechanism has been proposed for other systems, our work provides an evolutionary mechanism for a group of proteins with different functions that bear no sequence similarity. Our data also indicate that the addition of a structural element at the N terminus of the λ head–tail connector protein endows it with a distinctive protein interaction capability compared with many of its putative homologues.

Structural investigations of a Podoviridae streptococcus phage C1, implications for the mechanism of viral entry

“…It was found that the 120 residue N-terminal D1 is similar to the fold observed in a very ubiquitous family of bacteriophage proteins (Fig. 5), which form closed ring structures found as a part of the tail tube, neck, or baseplate (19). This β-sandwich fold is observed, for example, in a bacteriophage T4 baseplate protein gp27, lambda tail tube protein gpV, lambda neck protein gpU, and gpFII (48)(49)(50)(51).…”

“…The crystal structure of C1 knob protein, gp12, was determined to 3 Å resolution by X-ray crystallography. The small N-terminal domain of the C1 tail protein has a protein fold commonly found in neck and tail tube proteins of Sipho-and Myoviridae phages (19), but not previously found in Podoviridae phage proteins. Apart from the 120 residue N-terminal domain, the gp12 structure has a novel fold, which might also occur in knob proteins of φ29-like phages.…”

Baseplate assembly of phage Mu: Defining the conserved core components of contractile-tailed phages and related bacterial systems

“…The N-terminal domain of Tal displays the same structure as the BH2 proteins Mup44 and gp27 of phages Mu and T4. The N-terminal domain of Dit possesses a "tail tube-fold" (23) and HHpred searches with Mup43/BH1 proteins result in high-probability hits to the Pfam HMM corresponding to the tail tube-fold region of Dit (PF05709: Sipho_Tail). Gene order analysis also supports a functional similarity between Dit and BH1 proteins as their genes generally lie between the genes encoding the tapemeasure protein and BH2/Tal proteins.…”

Molecular architecture of tailed double-stranded DNA phages

“…All these proteins probably have a common evolutionary origin. 122,123 Structure of the peripheral part of the baseplate/tail-tip complexes vary in size and complexity, depending on specificity of phage-host interactions. However the receptor binding-proteins of phages, have common features.…”

“…144 Although the overall fold of gpU is somewhat different from that of the tail tube protein, gpV, a similar portion of the tertiary structure was detected in both proteins, suggesting their common evolutionary origin. 122 Myophage T4 has 2 terminator proteins: gp3, which (like gpU of phage λ) stops the polymerization of the tail tube, and gp15, which terminates the polymerization of the contractile sheath. 145 In the T4 virion, gp3 (175 residues) and gp15 (272 residues) make hexameric rings, with the gp3 ring located on top of the tail tube and the gp15 ring docked on top of gp3.…”