Molecular mechanism of leukocidin GH–integrin CD11b/CD18 recognition and species specificity (CROSBI ID 272882)
Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija
Podaci o odgovornosti
Trstenjak, Nikolina ; Milić, Dalibor ; Graewert, Melissa A. ; Rouha, Harald ; Svergun, Dmitri ; Djinović-Carugo, Kristina ; Nagy, Eszter ; Badarau, Adriana
engleski
Molecular mechanism of leukocidin GH–integrin CD11b/CD18 recognition and species specificity
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 poreforming 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.
host–pathogen interaction ; pore forming toxins ; receptor recognition ; leukocidin ; integrin
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Podaci o izdanju
117 (1)
2020.
317-327
objavljeno
0027-8424
10.1073/pnas.1913690116
Povezanost rada
Kemija, Biologija, Interdisciplinarne prirodne znanosti