Naslov
Molecular mechanism of leukocidin GH–integrin CD11b/CD18 recognition and species specificity

Autori
Trstenjak, Nikolina ; Milić, Dalibor ; Graewert, Melissa A. ; Rouha, Harald ; Svergun, Dmitri ; Djinović-Carugo, Kristina ; Nagy, Eszter ; Badarau, Adriana

Izvornik
Proceedings of the National Academy of Sciences (0027-8424) 117 (2020), 1; 317-327

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
host–pathogen interaction ; pore forming toxins ; receptor recognition ; leukocidin ; integrin

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija, Interdisciplinarne prirodne znanosti

POVEZANOST RADA