| Structural highlights
6rhw is a 3 chain structure with sequence from "micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885 and Human. 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, CD11B, CR3A (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
[ITAM_HUMAN] Genetic variations in ITGAM has been associated with susceptibility to systemic lupus erythematosus type 6 (SLEB6) [MIM:609939]. Systemic lupus erythematosus (SLE) is a chronic, inflammatory and often febrile multisystemic disorder of connective tissue. It affects principally the skin, joints, kidneys and serosal membranes. It is thought to represent a failure of the regulatory mechanisms of the autoimmune system.
Function
[ITAM_HUMAN] Integrin alpha-M/beta-2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles. 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 alpha-M/beta-2 is also a receptor for fibrinogen, factor X and ICAM1. It recognizes P1 and P2 peptides of fibrinogen gamma chain.
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.
References
- ↑ 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
|
