We specialize in constructing T4 display systems (SOC/HOC display) ideal for displaying large proteins or multi-subunit complexes that are challenging for M13 systems.
Creative Biolabs is a global leader in Phage Services, leveraging decades of experience to provide cutting-edge solutions for phage display, library construction, and genomic engineering. As a foundational model organism in molecular biology, the T4 bacteriophage (or T4 phage) remains a critical tool for modern biotechnology. Beyond T4, we offer comprehensive resources on other key model phages, including Lambda Phage, M13 Phage, T7 Phage, and MS2/RNA Phage. Our advanced platforms utilize the unique properties of T4 to facilitate high-throughput screening and the development of novel therapeutics and diagnostics.
The T4 bacteriophage is a dsDNA virus belonging to the family Straboviridae (formerly Myoviridae) within the order Caudovirales. It specifically infects Escherichia coli bacteria and is strictly lytic (virulent), meaning it does not integrate into the host genome to form a prophage. Historically, T4 has been instrumental in elucidating fundamental biological processes, including the nature of the genetic code, the existence of mRNA, and the mechanism of DNA replication.
In contemporary research, T4 is prized for its large genome (~169 kb), which allows for significant genetic manipulation. Its rapid replication cycle and robust capsid structure make it an excellent candidate for T4 Phage Display Systems, particularly for displaying large or complex proteins that cannot be accommodated by filamentous phages like M13.
The bacteriophage T4 structure is one of the most complex molecular machines known in virology. It consists of three primary components: a prolate icosahedral head, a contractile tail, and a specialized baseplate with tail fibers.
Fig.1 T4 bacteriophage structure.
The T4 bacteriophage life cycle is strictly lytic and rapid, typically completing within 25-30 minutes at 37°C. The process involves a highly coordinated sequence of events that repurposes the host's cellular machinery entirely for viral production.
The life cycle begins when the long tail fibers (LTF) recognize and bind reversibly to specific receptors on the E. coli surface, such as Lipopolysaccharide (LPS) or the outer membrane protein C (OmpC). This is followed by irreversible binding of the short tail fibers (STF) to the cell surface, triggering a conformational change in the baseplate.
The conformational change causes the tail sheath to contract, driving the rigid inner tube through the bacterial outer membrane and peptidoglycan layer. The viral DNA is then injected from the capsid into the host cytoplasm, while the protein coat remains outside.
Once inside, T4 immediate-early and delayed-early genes are expressed to halt host gene expression and degrade the host genome. The synthesized viral enzymes then replicate the phage DNA. Late genes are subsequently expressed to produce structural proteins (capsid, tail, fibers).
The T4 phage components assemble via three independent pathways: head assembly, tail assembly, and tail fiber assembly. The genomic DNA is packaged into the prohead via an ATP-dependent motor until the head is full ("headful packaging"). Finally, the filled heads join with the tails and fibers to form mature virions.
In the final stage, the phage produces holin and endolysin enzymes. Holin creates pores in the inner membrane, allowing endolysin to degrade the peptidoglycan cell wall. The host cell bursts (lyses), releasing approximately 100-150 new virions ready to infect adjacent bacteria.
The structural complexity of bacteriophage T4 has made it a subject of intense study for decades, serving as a primary model for understanding viral assembly and host recognition mechanisms. Recent advances in cryo-electron microscopy and X-ray crystallography have provided atomic-level insights into its sophisticated infection machinery. In a significant study, researchers successfully elucidated the crystal structure of the carboxy-terminal region of the T4 proximal long tail fiber protein (gp34). This specific region is critical for the stability of the fibrous network that facilitates the initial, reversible host recognition event on the bacterial surface.
The study revealed that gp34 forms a distinctive triple-helical neck that connects to an extended triple β-helix domain. This architectural arrangement provides a mechanical model explaining how the tail fibers withstand the significant shear forces encountered during adsorption. Furthermore, the data highlighted the presence of specific metal-ion binding sites within the structure that are essential for maintaining the integrity of the tail fibers under varying environmental conditions. These structural revelations are not merely academic; they provide a blueprint for engineering T4 tail fibers to alter host specificity. By modifying these recognition domains based on the crystallographic data, researchers can retarget T4 phages to bind non-native bacterial pathogens, thereby expanding the potential of phage therapy and precise bacterial detection assays.
Fig.2 Crystal structure of the carboxy-terminal region of gp34.1
Our platform offers a comprehensive suite of services centered around T4 phage technology, ranging from display systems to large-scale production.
We specialize in constructing T4 display systems (SOC/HOC display) ideal for displaying large proteins or multi-subunit complexes that are challenging for M13 systems.
Our team generates high-diversity cDNA or peptide libraries using T4 vectors, enabling the screening of high-affinity binders for diagnostic and therapeutic applications.
We provide high-titer, high-purity T4 phage preparations suitable for structural biology, genomic analysis, and assay development.
From environmental samples to clinical isolates, we offer end-to-end services for the isolation, enrichment, and purification of novel T4-like phages.
Q: Is the T4 phage lytic or lysogenic?
Q: What are the primary receptors for T4 phage?
A: T4 primarily utilizes the outer membrane protein C (OmpC) and lipopolysaccharides (LPS) on the surface of Escherichia coli as receptors for adsorption.
Q: Why is T4 used in phage display?
A: Unlike filamentous phages, T4 has a large capsid that can display multiple copies of large proteins or domains without disrupting viral assembly. This makes it ideal for vaccine development and studying complex protein interactions.
Q: How does T4 differ from T7 phage?
A: T4 is a complex myovirus with a contractile tail and a large genome (169 kb) encoding its own replication machinery, whereas T7 is a smaller podovirus with a short non-contractile tail and a simpler genome (~40 kb) that relies more heavily on efficient transcription by its own RNA polymerase.
Q: Is T4 phage safe to handle in the laboratory?
A: Yes, T4 bacteriophage specifically infects Escherichia coli bacteria and cannot infect human or animal cells. It is generally classified as a Risk Group 1 organism, making it safe for standard microbiological laboratory use with appropriate good laboratory practices.
Q: What is the packaging capacity of T4 display vectors?
A: Due to its "headful" packaging mechanism and large capsid size, T4 can accommodate larger DNA insertions compared to filamentous phages like M13. This allows for the display of larger peptides, complex protein domains, or even multi-subunit proteins on its surface.
Q: Can T4 phage exhibit lysis inhibition?
A: Yes, T4 exhibits a unique phenomenon called lysis inhibition (LIN). If a T4-infected cell is superinfected by another T4 phage, the lysis time is delayed significantly, allowing the phage to produce a much larger burst size (up to 400 virions) before releasing progeny.
Q: How should T4 phage preparations be stored?
A: T4 phage lysates are typically stable at 4°C for short-to-medium-term storage. For long-term preservation, they should be stored at -80°C with a cryoprotectant such as glycerol or DMSO to prevent damage to the complex tail structures during freeze-thaw cycles.
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