Structural basis for interactions between tenascins and lectican C-type lectin domains: evidence for a crosslinking role for tenascins.
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.
Department of Molecular Biophysics, Lund University, Box 124, S-221 00 Lund, Sweden.
Anna
A
Lundell
Anders I
AI
Olin
Matthias
M
Mörgelin
Salam
S
al-Karadaghi
Anders
A
Aspberg
Derek T
DT
Logan
D053674:Aggrecans; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D050260:Carbohydrate Metabolism; D003432:Cross-Linking Reagents / Q000737:chemistry; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019007:P-Selectin / Q000378:metabolism; D011485:Protein Binding; D011509:Proteoglycans / Q000378:metabolism*; D051381:Rats; D017386:Sequence Homology, Amino Acid; D019063:Tenascin / Q000378:metabolism*
C508321:Acan protein, rat; D053674:Aggrecans; D003432:Cross-Linking Reagents; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D019007:P-Selectin; D011509:Proteoglycans; D019063:Tenascin; C074638:tenascin R; D006820:Hyaluronic Acid; D002118:Calcium