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Lookup NU author(s): Professor David KavanaghORCiD
This is the authors' accepted manuscript of an article that has been published in its final definitive form by Nature Publishing Group, 2015.
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The serum protein complement factor H (FH) ensures downregulation of the complement alternative pathway, a branch of innate immunity, upon interaction with specific glycans on host cell surfaces. Using ligand-based NMR, we screened a comprehensive set of sialylated glycans for binding to FH and solved the crystal structure of a ternary complex formed by the two C-terminal domains of FH, a sialylated trisaccharide and the complement C3b thioester-containing domain. Key residues in the sialic acid binding site are conserved from mice to men, and residues linked to atypical hemolytic uremic syndrome cluster within this binding site, suggesting a possible role for sialic acid as a host marker also in other mammals and a critical role in human renal complement homeostasis. Unexpectedly, the FH sialic acid binding site is structurally homologous to the binding sites of two evolutionarily unrelated proteins. The crystal structure also advances our understanding of bacterial immune evasion strategies.
Author(s): Blaum BS, Hannan JP, Herbert AP, Kavanagh D, Uhrin D, Stehle T
Publication type: Article
Publication status: Published
Journal: Nature Chemical Biology
Print publication date: 01/01/2015
Online publication date: 24/11/2014
Acceptance date: 02/10/2014
Date deposited: 30/01/2015
ISSN (print): 1552-4450
ISSN (electronic): 1552-4469
Publisher: Nature Publishing Group
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