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@article{Gyapon-Quast:2021:10.4049/jimmunol.2000072,
author = {Gyapon-Quast, F and Goicoechea, de Jorge E and Malik, T and Wu, N and Yu, J and Chai, W and Feizi, T and Liu, Y and Pickering, MC},
doi = {10.4049/jimmunol.2000072},
journal = {Journal of Immunology},
pages = {534--541},
title = {Defining the glycosaminoglycan interactions of complement factor H-related protein 5},
url = {http://dx.doi.org/10.4049/jimmunol.2000072},
volume = {207},
year = {2021}
}

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TY  - JOUR
AB  - Complement activation is an important mediator of kidney injury in glomerulonephritis. Complement factor H (FH) and FH-related protein 5 (FHR-5) influence complement activation in C3 glomerulopathy and IgA nephropathy by differentially regulating glomerular complement. FH is a negative regulator of complement C3 activation. Conversely, FHR-5 in vitro promotes C3 activation either directly or by competing with FH for binding to complement C3b. The FH-C3b interaction is enhanced by surface glycosaminoglycans (GAGs) and the FH-GAG interaction is well-characterized. In contrast, the contributions of carbohydrates to the interaction of FHR-5 and C3b are unknown. Using plate-based and microarray technologies we demonstrate that FHR-5 interacts with sulfated GAGs and that this interaction is influenced by the pattern and degree of GAG sulfation. The FHR-5-GAG interaction that we identified has functional relevance as we could show that the ability of FHR-5 to prevent binding of FH to surface C3b is enhanced by surface kidney heparan sulfate. Our findings are important in understanding the molecular basis of the binding of FHR-5 to glomerular complement and the role of FHR-5 in complement-mediated glomerular disease.
AU  - Gyapon-Quast,F
AU  - Goicoechea,de Jorge E
AU  - Malik,T
AU  - Wu,N
AU  - Yu,J
AU  - Chai,W
AU  - Feizi,T
AU  - Liu,Y
AU  - Pickering,MC
DO  - 10.4049/jimmunol.2000072
EP  - 541
PY  - 2021///
SN  - 0022-1767
SP  - 534
TI  - Defining the glycosaminoglycan interactions of complement factor H-related protein 5
T2  - Journal of Immunology
UR  - http://dx.doi.org/10.4049/jimmunol.2000072
UR  - https://www.ncbi.nlm.nih.gov/pubmed/34193601
UR  - http://hdl.handle.net/10044/1/91561
VL  - 207
ER  -