7EVP

Cryo-EM structure of the Gp168-beta-clamp complex

Summary for 7EVP

• Entry DOI: 10.2210/pdb7evp/pdb
• EMDB information: 31339
• Descriptor: Beta sliding clamp, Sliding clamp inhibitor (2 entities in total)
• Functional Keywords: gp168, dna beta-clamp, cross-species inhibitor, antimicrobial protein
• Biological source: Staphylococcus aureus; More
• Total number of polymer chains: 4
• Total formula weight: 101906.79

Authors

Liu, B.,Li, S.,Liu, Y.,Chen, H.,Hu, Z.,Wang, Z.,Gou, L.,Zhang, L.,Ma, B.,Wang, H.,Matthews, S.,Wang, Y.,Zhang, K. (deposition date: 2021-05-21, release date: 2022-02-16, Last modification date: 2024-06-05)

Primary citation

Liu, B.,Li, S.,Liu, Y.,Chen, H.,Hu, Z.,Wang, Z.,Zhao, Y.,Zhang, L.,Ma, B.,Wang, H.,Matthews, S.,Wang, Y.,Zhang, K.
Bacteriophage Twort protein Gp168 is a beta-clamp inhibitor by occupying the DNA sliding channel.
Nucleic Acids Res., 49:11367-11378, 2021

PubMed Abstract: Bacterial chromosome replication is mainly catalyzed by DNA polymerase III, whose beta subunits enable rapid processive DNA replication. Enabled by the clamp-loading complex, the two beta subunits form a ring-like clamp around DNA and keep the polymerase sliding along. Given the essential role of β-clamp, its inhibitors have been explored for antibacterial purposes. Similarly, β-clamp is an ideal target for bacteriophages to shut off host DNA synthesis during host takeover. The Gp168 protein of phage Twort is such an example, which binds to the β-clamp of Staphylococcus aureus and prevents it from loading onto DNA causing replication arrest. Here, we report a cryo-EM structure of the clamp-Gp168 complex at 3.2-Å resolution. In the structure of the complex, the Gp168 dimer occupies the DNA sliding channel of β-clamp and blocks its loading onto DNA, which represents a new inhibitory mechanism against β-clamp function. Interestingly, the key residues responsible for this interaction on the β-clamp are well conserved among bacteria. We therefore demonstrate that Gp168 is potentially a cross-species β-clamp inhibitor, as it forms complex with the Bacillus subtilis β-clamp. Our findings reveal an alternative mechanism for bacteriophages to inhibit β-clamp and provide a new strategy to combat bacterial drug resistance.

PubMed: 34614154
DOI: 10.1093/nar/gkab875

Experimental method

ELECTRON MICROSCOPY (3.2 Å)