| Structural highlights
6rhv is a 3 chain structure with sequence from "micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885 and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| Gene: | lukG, ELQ85_15505, EP54_11070, EQ90_09460, HMPREF3211_02235, NCTC10654_02179, NCTC10702_03203, NCTC13131_01350, RK64_10675 ("Micrococcus aureus" (Rosenbach 1884) Zopf 1885), lukH, BTN44_11630, EP54_11065, EQ90_09455, HMPREF3211_02234, NCTC10654_02180, NCTC10702_03204, NCTC13131_01351, NCTC13196_01958, RK64_10680 ("Micrococcus aureus" (Rosenbach 1884) Zopf 1885), Itgam (LK3 transgenic mice) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[ITAM_MOUSE] Integrin ITGAM/ITGB2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles and pathogens (By similarity). It is identical with CR-3, the receptor for the iC3b fragment of the third complement component. It probably recognizes the R-G-D peptide in C3b. Integrin ITGAM/ITGB2 is also a receptor for fibrinogen, factor X and ICAM1. It recognizes P1 and P2 peptides of fibrinogen gamma chain. Regulates neutrophil migration. In association with beta subunit ITGB2/CD18, required for CD177-PRTN3-mediated activation of TNF primed neutrophils (By similarity). May regulate phagocytosis-induced apoptosis in extravasated neutrophils (By similarity). May play a role in mast cell development (By similarity). Required with TYROBP/DAP12 in microglia to control production of microglial superoxide ions which promote the neuronal apoptosis that occurs during brain development (PubMed:18685038).[UniProtKB:P11215][1] [2] [3] [4]
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[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wakselman S, Bechade C, Roumier A, Bernard D, Triller A, Bessis A. Developmental neuronal death in hippocampus requires the microglial CD11b integrin and DAP12 immunoreceptor. J Neurosci. 2008 Aug 6;28(32):8138-43. doi: 10.1523/JNEUROSCI.1006-08.2008. PMID:18685038 doi:http://dx.doi.org/10.1523/JNEUROSCI.1006-08.2008
- ↑ Coxon A, Rieu P, Barkalow FJ, Askari S, Sharpe AH, von Andrian UH, Arnaout MA, Mayadas TN. A novel role for the beta 2 integrin CD11b/CD18 in neutrophil apoptosis: a homeostatic mechanism in inflammation. Immunity. 1996 Dec;5(6):653-66. doi: 10.1016/s1074-7613(00)80278-2. PMID:8986723 doi:http://dx.doi.org/10.1016/s1074-7613(00)80278-2
- ↑ Tang T, Rosenkranz A, Assmann KJ, Goodman MJ, Gutierrez-Ramos JC, Carroll MC, Cotran RS, Mayadas TN. A role for Mac-1 (CDIIb/CD18) in immune complex-stimulated neutrophil function in vivo: Mac-1 deficiency abrogates sustained Fcgamma receptor-dependent neutrophil adhesion and complement-dependent proteinuria in acute glomerulonephritis. J Exp Med. 1997 Dec 1;186(11):1853-63. doi: 10.1084/jem.186.11.1853. PMID:9382884 doi:http://dx.doi.org/10.1084/jem.186.11.1853
- ↑ Rosenkranz AR, Coxon A, Maurer M, Gurish MF, Austen KF, Friend DS, Galli SJ, Mayadas TN. Impaired mast cell development and innate immunity in Mac-1 (CD11b/CD18, CR3)-deficient mice. J Immunol. 1998 Dec 15;161(12):6463-7. PMID:9862668
- ↑ Trstenjak N, Milic D, Graewert MA, 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 U S A. 2019 Dec 18. pii: 1913690116. doi:, 10.1073/pnas.1913690116. PMID:31852826 doi:http://dx.doi.org/10.1073/pnas.1913690116
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