CONSERVED BASIC RESIDUES IN THE C-TYPE LECTIN AND SHORT COMPLEMENT REPEAT DOMAINS OF THE G3 REGION OF PROTEOGLYCANS

Aggrecan is the major proteoglycan of the extracellular matrix in cart ilage. It contains two N-terminal globular regions, G1 and G2, and one C-terminal globular region, G3. G3 is implicated in the intracellular processing of aggrecan and contains a C-type lectin carbohydrate reco gnition domain (CRD), frequent occurrences of a C-terminal short compl ement repeat (SCR) domain, and occasionally an N-terminal epidermal gr owth factor domain. The CRD and SCR domains in 13 G3 sequences were ea ch subjected to structural analysis. Alignment of 131 sequences from a ll seven groups in the CRD superfamily defined a consensus length of 1 36 residues, in which 32 %, of residues were conserved. Although the G 3 CRD sequences agreed with this consensus, they also contained five f ully conserved basic residues that are atypical of the CRD superfamily . Homology modelling showed that four of these residues are located on a surface region on the CRD that is separate from the Ca2+-binding re sidues involved in carbohydrate interactions. One conserved basic resi due is identical in position with that of a conserved basic residue th at mediates hyaluronate binding in the structurally related proteoglyc an tandem repeat (PTR) domain in G1 and in link protein. The alignment of 13 G3 SCR sequences with 101 sequences in the SCR superfamily show ed good agreement with conserved residues in the SCR superfamily. Ther e are also five conserved basic residues in the G3 SCR that are atypic al of the SCR superfamily, and homology modelling showed that all five were located on one surface of the SCR. It is concluded that both the CRD and SCR domains in G3 possess basic residues that are atypical of their superfamilies and might be related to function, and that the G3 CRD domain shows an evolutionary relationship to the PTR domain in G1 .