The gp38 Adhesins of the T4 Superfamily: A Complex Modular Determinant of the Phage’s Host Specificity

Abstract

The tail fiber adhesins are the primary determinants of host range in the T4-type bacteriophages. Among the indispensable virion components, the sequences of the long tail fiber genes and their associated adhesins are among the most variable. The predominant form of the adhesin in the T4-type phages is not even the version of the gene encoded by T4, the archetype of the superfamily, but rather a small unrelated protein (gp38) encoded by closely related phages such as T2 and T6. This gp38 adhesin has a modular design: its N-terminal attachment domain binds at the tip of the tail fiber, whereas the C-terminal specificity domain determines its host receptor affinity. This specificity domain has a series of four hypervariable segments (HVSs) that are separated by a set of highly conserved glycine-rich motifs (GRMs) that apparently form the domain’s conserved structural core. The role of gp38’s various components was examined by a comparative analysis of a large series of gp38 adhesins from T-even superfamily phages with differing host specificities. A deletion analysis revealed that the individual HVSs and GRMs are essential to the T6 adhesin’s function and suggests that these different components all act in synergy to mediate adsorption. The evolutionary advantages of the modular design of the adhesin involving both conserved structural elements and multiple independent and easily interchanged specificity determinants are discussed.

Modified Bacteriophage S16 Long Tail Fiber Proteins for Rapid and Specific Immobilization and Detection of Salmonella Cells

“…The distal-tip adhesin gp38, common to many T-even phages, represents the actual interface for host cell recognition and binding (48). The modular design of gp38 proteins is comprised of a highly variable C-terminal domain composed of glycine-rich motifs (GRMs) interlaced with a series of hypervariable segments (HVSs).…”

“…The modular design of gp38 proteins is comprised of a highly variable C-terminal domain composed of glycine-rich motifs (GRMs) interlaced with a series of hypervariable segments (HVSs). The latter display high levels of plasticity (66) and are very susceptible to recombinational shuffling, which can modify the binding properties and, also, the phage host range (47,48). Ultimately, structural characterization of gp38 and identification of the HVS receptor binding sites could permit directed modification of LTFs to generate affinity molecules with improved binding properties or altered host specificities.…”

“…The C-terminal intramolecular chaperone domain of gp37 is then cleaved, prior to association of gp38 to its tip (43,48). The adhesin gp38 itself offers a modular design that includes a C-terminal specificity domain that determines the binding range of phage S16 (47,48).…”

Outer Membrane Proteins Ail and OmpF of Yersinia pestis Are Involved in the Adsorption of T7-Related Bacteriophage Yep-phi

“…OmpA protein plays a structural role in the integrity of the bacterial cell surface (36). It is proposed to interact specifically with the peptidoglycan layer (36) and serves as a receptor for several T-even phages infecting E. coli (31). OmpF is often regarded as a classical porin, which is present in large quan- tities, and is also required as a receptor by several phages of E. coli (31,36,37).…”

“…The lysis activity of each phage was examined using spot tests on Y. pestis strains (9,31). A series of exponential-phase cultures were prepared for each mutant strain.…”