Molecular Interactions between Complement Factor H and Its Heparin and Heparan Sulfate Ligands

UM > MA MAN KEI AND LO PAK SAM COLLEGE

Status	已發表Published
	Molecular Interactions between Complement Factor H and Its Heparin and Heparan Sulfate Ligands
	Perkins, SJ; Fung, K. W.; Khan, S
	2014-03-31
Source Publication	Frontiers in Immunology
ISSN	doi:10.3389.fimmu.2014.00126
Pages	doi:10.3389.fimmu.2014.00126-doi:10.3389.fimmu.2014.00126
Abstract	Complement factor H (CFH) is the major regulator of the central complement protein C3b in the alternative pathway of complement activation. A molecular view of the CFH interaction with native heparan sulfate (HS) is central for understanding the mechanism of how surface-bound CFH interacts with C3b bound to host cell surfaces. HS is composed of sulfated heparin-like S-regions that alternate with desulfated NA-regions. Solution structural studies of heparin (equivalent to the S-regions) and desulfated HS (the NA-regions) by scattering and ultracentrifugation showed that each structure was mostly extended and partially bent, but with greater bending and flexibility in the NA-regions compared to the S-regions. Their solution structures have been deposited in the Protein Data Bank. The largest HS oligosaccharides showed more bent and flexible structures than those for heparin. A folded-back domain structure for the solution structure of the 20 domains in CFH was determined likewise. CFH binds to the S-regions but less so to the NA-regions of HS. The bivalent interaction of CFH–heparin was observed by ultracentrifugation, and binding studies of CFH fragments with heparin-coated sensor chips. In common with other CFH interactions with its physiological and pathophysiological ligands, the CFH–heparin and CFH–C3b interactions have moderate micromolar dissociation constants KD, meaning that these complexes do not fully form in vivo. The combination of the solution structures and binding studies indicated a two-site interaction model of CFH with heparin at cell surfaces. By this, the bivalent binding of CFH to a cell surface is co-operative. Defective interactions at either of the two independent CFH–heparin sites reduce the CFH interaction with surface-bound C3b and lead to immune disorders.
Keyword	Complement system Factor H Heparin Heparan Sulfate
URL	View the original
Language	英語English
The Source to Article	PB_Publication
PUB ID	58721
Document Type	Journal article
Collection	MA MAN KEI AND LO PAK SAM COLLEGE
Corresponding Author	Perkins, SJ
Recommended Citation GB/T 7714	Perkins, SJ,Fung, K. W.,Khan, S. Molecular Interactions between Complement Factor H and Its Heparin and Heparan Sulfate Ligands[J]. Frontiers in Immunology, 2014, doi:10.3389.fimmu.2014.00126-doi:10.3389.fimmu.2014.00126.
APA	Perkins, SJ., Fung, K. W.., & Khan, S (2014). Molecular Interactions between Complement Factor H and Its Heparin and Heparan Sulfate Ligands. Frontiers in Immunology, doi:10.3389.fimmu.2014.00126-doi:10.3389.fimmu.2014.00126.
MLA	Perkins, SJ,et al."Molecular Interactions between Complement Factor H and Its Heparin and Heparan Sulfate Ligands".Frontiers in Immunology (2014):doi:10.3389.fimmu.2014.00126-doi:10.3389.fimmu.2014.00126.

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