Link protein and aggrecan of the extracellular matrix each contain two proteoglycan tandem repeat (PTR) domains that interact with hyaluronate. Consensus secondary structure predictions for 59 PTR sequences and 129 C-type lectin sequences give similar patterns of two α-helices and up to seven β-strands. Protein fold recognition analyses show that the 59 PTR sequences are highly compatible with the C-type lectin crystal structure. The predicted fold consists of a conserved motif formed from an antiparallel β-sheet flanked by two α-helices, the motif being attached to two distinct types of β-sheet region in the two superfamilies. Arg9 or Lys11 on an exposed loop and up to three other Arg residues in the β-sheet region are conserved and may form part of a hyaluronate binding site.