4ONT

Ternary host recognition complex of complement factor H, C3d, and sialic acid

Summary for 4ONT

• Entry DOI: 10.2210/pdb4ont/pdb
• Descriptor: Complement factor H, Complement C3d fragment, N-acetyl-alpha-neuraminic acid-(2-3)-beta-D-galactopyranose-(1-4)-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: complement control protein, ccp, short consensus repeat, scr, sushi domain, complement regulation, sialic acid, host glycan, host cell surface, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P08603 P01024
• Total number of polymer chains: 6
• Total formula weight: 153200.01

Authors

Blaum, B.S.,Stehle, T.S. (deposition date: 2014-01-29, release date: 2014-11-26, Last modification date: 2024-11-20)

Primary citation

Blaum, B.S.,Hannan, J.P.,Herbert, A.P.,Kavanagh, D.,Uhrin, D.,Stehle, T.
Structural basis for sialic acid-mediated self-recognition by complement factor H.
Nat.Chem.Biol., 11:77-82, 2015

PubMed 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.

PubMed: 25402769
DOI: 10.1038/nchembio.1696

Experimental method

X-RAY DIFFRACTION (2.15 Å)