PDBsum entry 1tdq

Extracellular matrix

PDB id: 1tdq

Contents

Protein chains

271 a.a. *

126 a.a. *

Metals

_CA ×3

Waters ×38

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Structural basis for interactions between tenascins and lectican c-Type lectin domains: evidence for a crosslinking role for tenascins.

Authors

A.Lundell, A.I.Olin, M.Mörgelin, S.Al-Karadaghi, A.Aspberg, D.T.Logan.

Ref.

Structure, 2004, 12, 1495-1506. [DOI no: 10.1016/j.str.2004.05.021]

PubMed id

15296743

Abstract

The C-terminal G3 domains of lecticans mediate crosslinking to diverse extracellular matrix (ECM) proteins during ECM assembly, through their C-type lectin (CLD) subdomains. The structure of the rat aggrecan CLD in a Ca(2+)-dependent complex with fibronectin type III repeats 3-5 of rat tenascin-R provides detailed support for such crosslinking. The CLD loops bind Ca2+ like other CLDs, but no carbohydrate binding is observed or possible. This is thus the first example of a direct Ca(2+)-dependent protein-protein interaction of a CLD. Surprisingly, tenascin-R does not coordinate the Ca2+ ions directly. Electron microscopy confirms that full-length tenascin-R and tenascin-C crosslink hyaluronan-aggrecan complexes. The results are significant for the binding of all lectican CLDs to tenascin-R and tenascin-C. Comparison of the protein interaction surface with that of P-selectin in complex with the PGSL-1 peptide suggests that direct protein-protein interactions of Ca(2+)-binding CLDs may be more widespread than previously appreciated.

Figure 2.
Figure 2. Overall Structure of the Complex between the Aggrecan CLD and FnIII Repeats 3–5 of Tenascin-R, TN3–5
A consistent coloring scheme is used throughout for the different domains. Surfaces, cartoon elements, and carbon atoms from domain 3 are colored beige, those in domain 4 are colored cyan, and those in domain 5 are purple. Figure 2, Figure 3, Figure 4 and Figure 7 were made using Pymol (http://www.pymol.org).
(A) Secondary structure cartoon. The three Ca^2+ ions are shown as yellow spheres. The boxes marked a–c denote the interaction areas for which detailed views are given in Figures 4A–4C.
(B) Surface representation colored by domain.
(C) Exploded “open book” view of the interaction surface. The aggrecan CLD has been rotated 90° around a horizontal axis in the plane of the paper, TN3–5 in the opposite direction. The cyan and purple patches on the surface of the CLD represent the interaction areas with TN4 and TN5, respectively. Similarly, the maroon patches on the surface of TN3–5 represent the interaction area with the CLD.
(D) The aggrecan CLD amino acid residues mediating interaction with tenascin-R form a surface corresponding to the sulfopeptide binding surface of P-selectin in complex with PSGL-1 (Somers et al., 2000). The interaction surface of P-selectin with the protein part of the PSGL-1 sulfoglycopeptide on is colored cyan, and the carbohydrate interaction surface is colored purple. The part of the PSGL-1 peptide visible in the crystal structure is shown as a ball-and-stick model. The figure is in the same orientation as the lower part of Figure 2C, showing the interaction surface of tenascin-R on aggrecan.

Figure 4.
Figure 4. Details of the Interactions between the Aggrecan CLD and TN3–5
Important interacting side chains are shown as ball-and-stick, and the central hydrogen bonds are highlighted. The color scheme is as described in the legend to Figure 2.
(A) Molecular interactions of the hydrophobic patch on loop L4 of the aggrecan CLD. The view is approximately the same as in Figure 2A.
(B) Interactions involving the CC′ loop in TN4. The view is approximately as in (A).
(C) Interactions of the TN4–5 linker region and the FG loop on TN5. The molecule has been rotated by approximately 180° around a vertical axis to make the interactions clearer; i.e., the view is from the back of the molecule as seen in Figure 2A.

The above figures are reprinted by permission from Cell Press: Structure (2004, 12, 1495-1506) copyright 2004.