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| Item Type: | Article |
|---|---|
| Title: | Structural insights into the activation mechanism of antimicrobial GBP1 |
| Creators Name: | Weismehl, M., Chu, X., Kutsch, M., Lauterjung, P., Herrmann, C., Kudryashev, M. and Daumke, O. |
| Abstract: | The dynamin-related human guanylate-binding protein 1 (GBP1) mediates host defenses against microbial pathogens. Upon GTP binding and hydrolysis, auto-inhibited GBP1 monomers dimerize and assemble into soluble and membrane-bound oligomers, which are crucial for innate immune responses. How higher-order GBP1 oligomers are built from dimers, and how assembly is coordinated with nucleotide-dependent conformational changes, has remained elusive. Here, we present cryo-electron microscopy-based structural data of soluble and membrane-bound GBP1 oligomers, which show that GBP1 assembles in an outstretched dimeric conformation. We identify a surface-exposed helix in the large GTPase domain that contributes to the oligomerization interface, and we probe its nucleotide- and dimerization-dependent movements that facilitate the formation of an antimicrobial protein coat on a gram-negative bacterial pathogen. Our results reveal a sophisticated activation mechanism for GBP1, in which nucleotide-dependent structural changes coordinate dimerization, oligomerization, and membrane binding to allow encapsulation of pathogens within an antimicrobial protein coat. |
| Keywords: | Dynamin Superfamily, Electron Microscopy, Guanylate-Binding Proteins, GTPase, Oligomerization |
| Source: | EMBO Journal |
| ISSN: | 0261-4189 |
| Publisher: | Springer Nature |
| Volume: | 43 |
| Number: | 4 |
| Page Range: | 615-636 |
| Date: | 15 February 2024 |
| Official Publication: | https://doi.org/10.1038/s44318-023-00023-y |
| PubMed: | View item in PubMed |
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