6RHV
Crystal structure of mouse CD11b I-domain (CD11b-I) in complex with Staphylococcus aureus octameric bi-component leukocidin LukGH (LukH K319A mutant)
Summary for 6RHV
| Entry DOI | 10.2210/pdb6rhv/pdb |
| Descriptor | Beta-channel forming cytolysin, Integrin alpha-M, DIMETHYL SULFOXIDE, ... (6 entities in total) |
| Functional Keywords | leukocidin, pore-forming toxin, octamer, receptor, complex, toxin |
| Biological source | Staphylococcus aureus More |
| Total number of polymer chains | 3 |
| Total formula weight | 95886.06 |
| Authors | Trstenjak, N.,Milic, D.,Djinovic-Carugo, K.,Badarau, A. (deposition date: 2019-04-23, release date: 2019-12-18, Last modification date: 2024-01-24) |
| Primary citation | Trstenjak, N.,Milic, D.,Graewert, M.A.,Rouha, H.,Svergun, D.,Djinovic-Carugo, K.,Nagy, E.,Badarau, A. Molecular mechanism of leukocidin GH-integrin CD11b/CD18 recognition and species specificity. Proc.Natl.Acad.Sci.USA, 117:317-327, 2020 Cited by PubMed Abstract: Host-pathogen interactions are central to understanding microbial pathogenesis. The staphylococcal pore-forming cytotoxins hijack important immune molecules but little is known about the underlying molecular mechanisms of cytotoxin-receptor interaction and host specificity. Here we report the structures of a staphylococcal pore-forming cytotoxin, leukocidin GH (LukGH), in complex with its receptor (the α-I domain of complement receptor 3, CD11b-I), both for the human and murine homologs. We observe 2 binding interfaces, on the LukG and the LukH protomers, and show that human CD11b-I induces LukGH oligomerization in solution. LukGH binds murine CD11b-I weakly and is inactive toward murine neutrophils. Using a LukGH variant engineered to bind mouse CD11b-I, we demonstrate that cytolytic activity does not only require binding but also receptor-dependent oligomerization. Our studies provide an unprecedented insight into bicomponent leukocidin-host receptor interaction, enabling the development of antitoxin approaches and improved animal models to explore these approaches. PubMed: 31852826DOI: 10.1073/pnas.1913690116 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.29 Å) |
Structure validation
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