Structural Basis for Interactions Between Tenascins and Lectican C-type Lectin Domains: Evidence for a Crosslinking Role for Tenascins

Structure. 2004 Aug;12(8):1495-506. doi: 10.1016/j.str.2004.05.021.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggrecans
  • Amino Acid Sequence
  • Animals
  • Calcium / metabolism*
  • Carbohydrate Metabolism
  • Cross-Linking Reagents / chemistry
  • Extracellular Matrix Proteins / metabolism*
  • Hyaluronic Acid / metabolism
  • Lectins, C-Type / metabolism*
  • Microscopy, Electron, Transmission
  • Models, Molecular*
  • Molecular Sequence Data
  • P-Selectin / metabolism
  • Protein Binding
  • Proteoglycans / metabolism*
  • Rats
  • Sequence Homology, Amino Acid
  • Tenascin / metabolism*

Substances

  • Acan protein, rat
  • Aggrecans
  • Cross-Linking Reagents
  • Extracellular Matrix Proteins
  • Lectins, C-Type
  • P-Selectin
  • Proteoglycans
  • Tenascin
  • tenascin R
  • Hyaluronic Acid
  • Calcium

Associated data

  • PDB/1TDQ