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 cartilage. 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 recognition domain (CRD), frequent occurrences of a C-terminal short complement repeat (SCR) domain, and occasionally an N-terminal epidermal growth factor domain. The CRD and SCR domains in 13 G3 sequences were each subjected to structural analysis. Alignment of 131 sequences from all seven groups in the CRD superfamily defined a consensus length of 136 residues, in which 32% of residues were conserved. Although the G3 CRD sequences agreed with this consensus, they also contained five fully 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 residues involved in carbohydrate interactions. One conserved basic residue is identical in position with that of a conserved basic residue that mediates hyaluronate binding in the structurally related proteoglycan tandem repeat (PTR) domain in G1 and in link protein. The alignment of 13 G3 SCR sequences with 101 sequences in the SCR superfamily showed good agreement with conserved residues in the SCR superfamily. There are also five conserved basic residues in the G3 SCR that are atypical 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.
Brissett
N C
NC
Department of Biochemistry and Molecular Biology, Royal Free Hospital School of Medicine, Rowland Hill Street, London NW3 2PF, U. K.
Perkins
S J
SJ
D053674:Aggrecans; D000595:Amino Acid Sequence; D050260:Carbohydrate Metabolism; D017124:Conserved Sequence; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011509:Proteoglycans / Q000737:chemistry* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity
D053674:Aggrecans; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans