PDBsum entry 1o7c

Cell adhesion

PDB id: 1o7c

Contents

Protein chain

98 a.a. *

* Residue conservation analysis

PDB id:

1o7c

Name:

Cell adhesion

Title:

Solution structure of the human tsg-6 link module in the presence of a hyaluronan octasaccharide

Structure:

Tumor necrosis factor-inducible protein tsg-6. Chain: t. Fragment: link_module, residues 36-133. Synonym: human tsg-6, hyaluronate-binding protein, tnf-stimulated gene 6 protein. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008. Other_details: extracellular, inflammation-associated

NMR struc:

20 models

Authors:

C.D.Blundell,P.Teriete,J.D.Kahmann,A.R.Pickford,I.D.Campbell,A.J.Day

Key ref:

C.D.Blundell et al. (2003). The link module from ovulation- and inflammation-associated protein TSG-6 changes conformation on hyaluronan binding. J Biol Chem, 278, 49261-49270. PubMed id: 12972412 DOI: 10.1074/jbc.M309623200

Date:

29-Oct-02 Release date: 23-Oct-03

Protein chain

P98066  (TSG6_HUMAN) -  Tumor necrosis factor-inducible gene 6 protein from Homo sapiens

Seq: 277 a.a.

Struc: 98 a.a.

Enzyme reactions

• Enzyme class: E.C.3.1.1.- - ?????

DOI no: 10.1074/jbc.M309623200

J Biol Chem 278:49261-49270 (2003)

PubMed id: 12972412

The link module from ovulation- and inflammation-associated protein TSG-6 changes conformation on hyaluronan binding.

C.D.Blundell, D.J.Mahoney, A.Almond, P.L.DeAngelis, J.D.Kahmann, P.Teriete, A.R.Pickford, I.D.Campbell, A.J.Day.

ABSTRACT

The solution structure of the Link module from human TSG-6, a hyaladherin with important roles in inflammation and ovulation, has been determined in both its free and hyaluronan-bound conformations. This reveals a well defined hyaluronan-binding groove on one face of the Link module that is closed in the absence of ligand. The groove is lined with amino acids that have been implicated in mediating the interaction with hyaluronan, including two tyrosine residues that appear to form essential intermolecular hydrogen bonds and two basic residues capable of supporting ionic interactions. This is the first structure of a non-enzymic hyaladherin in its active state, and identifies a ligand-induced conformational change that is likely to be conserved across the Link module superfamily. NMR and isothermal titration calorimetry experiments with defined oligosaccharides have allowed us to infer the minimum length of hyaluronan that can be accommodated within the binding site and its polarity in the groove; these data have been used to generate a model of the complex formed between the Link module and a hyaluronan octasaccharide.

Selected figure(s)

Figure 2.
FIG. 2. Solution structures of the TSG-6 Link module in its free (A and B) and HA[8]-bound states (C and D). A and C, stereoviews of backbone traces for the family of 20 structures superimposed on the backbone heavy atoms in the secondary structure elements. B and D, secondary structure organization of the Link module, shown on the lowest energy structure of each family. The fold consists of two antiparallel -sheets SI (light blue; residues 2-6 ( 1), 29-31 ( 2), and 89-93 ( 6)) and SII (dark blue; residues 49-52 ( 3), 56-61 ( 4), and 74-77 ( 5)), connected in a parallel arrangement by two H-bonds between strands 3 and 6 (see Supplemental Material Fig. S1) and two helices (residues 16-25 ( 1) and 33-42 ( 2)) shown in red.

Figure 6.
FIG. 6. The interaction of HA with the TSG-6 Link module induces the opening of the binding groove. A and B, atomic spheres depiction of the lowest energy free (closed) and HA[8]-bound (open) structures, in the same orientation, with the bottom portion of each structure are shown in a ribbon representation. The conformational change of the 4- 5 loop opens a groove, exposing the key HA-binding residues (red); the binding site can be extended by mutation of Glu6 (green) to Lys, resulting in a higher affinity interaction with HA. The closed (A) and open (B) states differ principally in the geometry of the disulfide bridge (sulfur atoms in yellow) linking the 4- 5 loop (Cys68) to the rigid connection between 2 and 4 (Cys47), as shown by sticks in C and D. E and F, the open groove, which is lined with atoms that experience significant shift perturbations on ligand binding (red), can accommodate an HA octasaccharide (blue sticks and green atomic spheres) in a favorable geometry without serious steric clashes; one possible conformation of HA is shown. The polarity and register were determined as described in text (see Fig. 7). F is rotated 90° toward the reader around the horizontal axis relative to E.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 49261-49270) copyright 2003.

Figures were selected by an automated process.