PDBsum entry 2d39

Immune system

PDB id: 2d39

Contents

Protein chain

209 a.a. *

Metals

_CA ×2

Waters ×283

* Residue conservation analysis

PDB id:

2d39

Name:

Immune system

Title:

Trivalent recognition unit of innate immunity system; crystal structure of human m-ficolin fibrinogen-like domain

Structure:

Ficolin-1. Chain: a, b, c. Fragment: fibrinogen like domain. Synonym: collagen/fibrinogen domain-containing protein 1, ficolin-a, ficolin a, m-ficolin. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: pichia pastoris. Expression_system_taxid: 4922.

Biol. unit:

Trimer (from PQS)

Resolution:

1.90Å R-factor: 0.209 R-free: 0.240

Authors:

M.Tanio,S.Kondo,S.Sugio,T.Kohno

Key ref:

M.Tanio et al. (2007). Trivalent recognition unit of innate immunity system: crystal structure of trimeric human M-ficolin fibrinogen-like domain. J Biol Chem, 282, 3889-3895. PubMed id: 17148457 DOI: 10.1074/jbc.M608627200

Date:

26-Sep-05 Release date: 12-Dec-06

Protein chains

O00602  (FCN1_HUMAN) -  Ficolin-1 from Homo sapiens

Seq: 326 a.a.

Struc: 209 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1074/jbc.M608627200

J Biol Chem 282:3889-3895 (2007)

PubMed id: 17148457

Trivalent recognition unit of innate immunity system: crystal structure of trimeric human M-ficolin fibrinogen-like domain.

M.Tanio, S.Kondo, S.Sugio, T.Kohno.

ABSTRACT

Ficolins are a kind of pathogen-recognition molecule in the innate immune systems. To investigate the discrimination mechanism between self and non-self by ficolins, we determined the crystal structure of the human M-ficolin fibrinogen-like domain (FD1), which is the ligand-binding domain, at 1.9A resolution. Although the FD1 monomer shares a common fold with the fibrinogen gamma fragment and tachylectin-5A, the Asp-282-Cys-283 peptide bond, which is the predicted ligand-binding site on the C-terminal P domain, is a normal trans bond, unlike the cases of the other two proteins. The trimeric formation of FD1 results in the separation of the three P domains, and the spatial arrangement of the three predicted ligand-binding sites on the trimer is very similar to that of the trimeric collectin, indicating that such an arrangement is generally required for pathogen-recognition. The ligand binding study of FD1 in solution indicated that the recombinant protein binds to N-acetyl-d-glucosamine and the peptide Gly-Pro-Arg-Pro and suggested that the ligand-binding region exhibits a conformational equilibrium involving cis-trans isomerization of the Asp-282-Cys-283 peptide bond. The crystal structure and the ligand binding study of FD1 provide an insight of the self- and non-self discrimination mechanism by ficolins.

Selected figure(s)

Figure 3.
FIGURE 3. The conserved disulfide bond and Ca^2+-binding region in the P domain. A, the Ca^2+-binding loop is stabilized by the conserved disulfide bond between Cys-270 and Cys-283. B, the 2F^o - F^c electron density is contoured at 1 at the region between Asp-282 and His-284. The Asp-282–Cys-283 peptide bond is in the normal trans configuration (arrow). C, the 2F^o - F^c electron density is contoured at 1.7 at the calcium-binding site. The Ca^2+ is shown as a yellow sphere.

Figure 6.
FIGURE 6. Arrangements of the ligand-binding sites of FD1 and MBL. Top (A) and side (B) views of arrangements of the ligand-binding sites on the FD1 trimer (magenta) and rat MBL (Protein Data Bank code 1KWV (48); slate). His-284, located on the predicted ligand-binding site in FD1, and the bound GlcNAc in rat MBL are shown as green spheres. The three binding sites of each trimer sit on the vertices of an equilateral triangle with each side about 50 Å in length.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2007, 282, 3889-3895) copyright 2007.

Figures were selected by an automated process.