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Publication Abstract from PubMed

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 alpha-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.

Molecular mechanism of leukocidin GH-integrin CD11b/CD18 recognition and species specificity.,Trstenjak N, Milic D, Graewert MA, Rouha H, Svergun D, Djinovic-Carugo K, Nagy E, Badarau A Proc Natl Acad Sci U S A. 2019 Dec 18. pii: 1913690116. doi:, 10.1073/pnas.1913690116. PMID:31852826^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.