6xz6
From Proteopedia
Structure of the trypanosome brucei factor H receptor bound to domain D5 of bovine factor H
Structural highlights
Function[CFAH_BOVIN] Glycoprotein that plays an essential role in maintaining a well-balanced immune response by modulating complement activation. Acts as a soluble inhibitor of complement, where its binding to self markers such as glycan structures prevents complement activation and amplification on cell surfaces. Accelerates the decay of the complement alternative pathway (AP) C3 convertase C3bBb, thus preventing local formation of more C3b, the central player of the complement amplification loop. As a cofactor of the serine protease factor I, CFH also regulates proteolytic degradation of already-deposited C3b. In addition, mediates several cellular responses through interaction with specific receptors. For example, interacts with CR3/ITGAM receptor and thereby mediates the adhesion of human neutrophils to different pathogens. In turn, these pathogens are phagocytosed and destroyed.[UniProtKB:P08603] Publication Abstract from PubMedPersistent pathogens have evolved to avoid elimination by the mammalian immune system including mechanisms to evade complement. Infections with African trypanosomes can persist for years and cause human and animal disease throughout sub-Saharan Africa. It is not known how trypanosomes limit the action of the alternative complement pathway. Here we identify an African trypanosome receptor for mammalian factor H, a negative regulator of the alternative pathway. Structural studies show how the receptor binds ligand, leaving inhibitory domains of factor H free to inactivate complement C3b deposited on the trypanosome surface. Receptor expression is highest in developmental stages transmitted to the tsetse fly vector and those exposed to blood meals in the tsetse gut. Receptor gene deletion reduced tsetse infection, identifying this receptor as a virulence factor for transmission. This demonstrates how a pathogen evolved a molecular mechanism to increase transmission to an insect vector by exploitation of a mammalian complement regulator. A receptor for the complement regulator factor H increases transmission of trypanosomes to tsetse flies.,Macleod OJS, Bart JM, MacGregor P, Peacock L, Savill NJ, Hester S, Ravel S, Sunter JD, Trevor C, Rust S, Vaughan TJ, Minter R, Mohammed S, Gibson W, Taylor MC, Higgins MK, Carrington M Nat Commun. 2020 Mar 12;11(1):1326. doi: 10.1038/s41467-020-15125-y. PMID:32165615[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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