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Structural basis for sialic acid-mediated self-recognition by complement factor H

Lookup NU author(s): Professor David KavanaghORCiD

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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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Abstract

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.

Publication metadata

Author(s): Blaum BS, Hannan JP, Herbert AP, Kavanagh D, Uhrin D, Stehle T

Publication type: Article

Publication status: Published

Journal: Nature Chemical Biology

Year: 2015

Volume: 11

Issue: 1

Pages: 77-82

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

URL: http://dx.doi.org/10.1038/NCHEMBIO.1696

DOI: 10.1038/NCHEMBIO.1696

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