PDBsum entry 4ont

Immune system

PDB id: 4ont

Contents

Protein chains

124 a.a.

295 a.a.

Ligands

BGC-GAL-SIA ×3

GOL ×7

Waters ×489

PDB id:

4ont

Name:

Immune system

Title:

Ternary host recognition complex of complement factor h, c3d, and sialic acid

Structure:

Complement factor h. Chain: f, d, e. Fragment: sushi 19-20 domains (unp residues 1107-1231). Synonym: h factor 1. Engineered: yes. Complement c3d fragment. Chain: a, b, c. Fragment: unp residues 996-1303. Synonym: c3d.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: cfh, hf, hf1, hf2. Expressed in: komagataella pastoris. Expression_system_taxid: 4922. Gene: c3, cpamd1. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.15Å R-factor: 0.175 R-free: 0.223

Authors:

B.S.Blaum,T.S.Stehle

Key ref:

B.S.Blaum et al. (2015). Structural basis for sialic acid-mediated self-recognition by complement factor H. Nat Chem Biol, 11, 77-82. PubMed id: 25402769 DOI: 10.1038/nchembio.1696

Date:

29-Jan-14 Release date: 26-Nov-14

Protein chains

P08603  (CFAH_HUMAN) -  Complement factor H from Homo sapiens

Seq: 1231 a.a.

Struc: 124 a.a.

Protein chains

P01024  (CO3_HUMAN) -  Complement C3 from Homo sapiens

Seq: 1663 a.a.

Struc: 295 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

DOI no: 10.1038/nchembio.1696

Nat Chem Biol 11:77-82 (2015)

PubMed id: 25402769

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

B.S.Blaum, J.P.Hannan, A.P.Herbert, D.Kavanagh, D.Uhrín, T.Stehle.

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.