PDBsum entry 2jhh

Sugar binding protein

PDB id: 2jhh

Contents

Protein chain

208 a.a. *

Metals

_CA ×2

Waters ×255

* Residue conservation analysis

PDB id:

2jhh

Name:

Sugar binding protein

Title:

Structure of globular heads of m-ficolin at acidic ph

Structure:

Ficolin-1. Chain: c, f. Fragment: c-terminal domain, residues 109-326. Synonym: ficolin-a, ficolin-alpha, m-ficolin, collagen/ fibrinogen domain-containing protein 1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_cell_line: high five.

Resolution:

1.70Å R-factor: 0.221 R-free: 0.252

Authors:

V.Garlatti,L.Martin,E.Gout,J.B.Reiser,G.J.Arlaud,N.M.Thielens, C.Gaboriaud

Key ref:

V.Garlatti et al. (2007). Structural basis for innate immune sensing by M-ficolin and its control by a pH-dependent conformational switch. J Biol Chem, 282, 35814-35820. PubMed id: 17897951 DOI: 10.1074/jbc.M705741200

Date:

22-Feb-07 Release date: 09-Oct-07

Protein chains

O00602  (FCN1_HUMAN) -  Ficolin-1 from Homo sapiens

Seq: 326 a.a.

Struc: 208 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1074/jbc.M705741200

J Biol Chem 282:35814-35820 (2007)

PubMed id: 17897951

Structural basis for innate immune sensing by M-ficolin and its control by a pH-dependent conformational switch.

V.Garlatti, L.Martin, E.Gout, J.B.Reiser, T.Fujita, G.J.Arlaud, N.M.Thielens, C.Gaboriaud.

ABSTRACT

Ficolins are soluble oligomeric proteins with lectin-like activity, assembled from collagen fibers prolonged by fibrinogen-like recognition domains. They act as innate immune sensors by recognizing conserved molecular markers exposed on microbial surfaces and thereby triggering effector mechanisms such as enhanced phagocytosis and inflammation. In humans, L- and H-ficolins have been characterized in plasma, whereas a third species, M-ficolin, is secreted by monocytes and macrophages. To decipher the molecular mechanisms underlying their recognition properties, we previously solved the structures of the recognition domains of L- and H-ficolins, in complex with various model ligands (Garlatti, V., Belloy, N., Martin, L., Lacroix, M., Matsushita, M., Endo, Y., Fujita, T., Fontecilla-Camps, J. C., Arlaud, G. J., Thielens, N. M., and Gaboriaud, C. (2007) EMBO J. 24, 623-633). We now report the ligand-bound crystal structures of the recognition domain of M-ficolin, determined at high resolution (1.75-1.8 A), which provides the first structural insights into its binding properties. Interaction with acetylated carbohydrates differs from the one previously described for L-ficolin. This study also reveals the structural determinants for binding to sialylated compounds, a property restricted to human M-ficolin and its mouse counterpart, ficolin B. Finally, comparison between the ligand-bound structures obtained at neutral pH and nonbinding conformations observed at pH 5.6 reveals how the ligand binding site is dislocated at acidic pH. This means that the binding function of M-ficolin is subject to a pH-sensitive conformational switch. Considering that the homologous ficolin B is found in the lysosomes of activated macrophages (Runza, V. L., Hehlgans, T., Echtenacher, B., Zahringer, U., Schwaeble, W. J., and Mannel, D. N. (2006) J. Endotoxin Res. 12, 120-126), we propose that this switch could play a physiological role in such acidic compartments.

Selected figure(s)

Figure 2.
FIGURE 2. The S1 ligand binding site in M-ficolin, TL5A, and L-ficolin. A–C, detailed views of the interactions of GalNAc, GlcNAc, and Neu5Ac in site S1 of M-ficolin. D, superposition of the ligand-free and three ligand-bound structures of M-ficolin showing that Tyr^271 is the only mobile component in site S1. E, interaction of GlcNAc in the homologous S1 binding site of tachylectin 5A (14). F, superposition of the S1 binding sites of M-ficolin (magenta) and L-ficolin (green). In L-ficolin, steric hindrance (as shown by black lines) prevents accommodation of large ligands such as Neu5Ac.

Figure 3.
FIGURE 3. The pH-dependent conformational switch observed in M-ficolin. A, the active binding conformation of site S1 observed at neutral pH involves residues contributed by four external loops. B, nonbinding conformation of site S1 observed at pH 5.6. The structure determined in this study (cyan, lacking the disordered segment 278–285) and subunit C of the structure reported previously by Tanio et al. (18) (orange) are superposed. The acidic pH destabilizes the four loops and dislocates the S1 site. C, superposition of the binding (magenta) and nonbinding (cyan) conformations determined in this study, illustrating the essential histidine-mediated stabilizations of the binding conformation (magenta) that are lost at acidic pH. The red dashed lines represent hydrogen bonds.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2007, 282, 35814-35820) copyright 2007.

Figures were selected by an automated process.