Identification and synthesis of a recognition signal for the attachment of glycosaminoglycans to proteins.
Comparison of the amino acid sequences of three different proteoglycan core proteins reveals a 12-amino acid sequence that is about 50% homologous among these proteoglycans. In each of the proteoglycans, this sequence surrounds the serine-glycine dipeptide in which the serine is known or presumed to be substituted with a chondroitin/dermatan sulfate glycosaminoglycan chain. Peptides containing this sequence from two proteoglycans were examined for their ability to serve as acceptors for xylosyltransferase, the enzyme that begins the assembly of glycosaminoglycan chains. Those peptides corresponding to amino acid sequences known to contain glycosaminoglycan-substituted serine residues in the protein were efficient xylosyltransferase acceptors, whereas peptides from sequences with no glycosaminoglycan-substituted serine residues were not. Amino acid substitutions at four critical sites in the acceptor peptides showed that single substitutions could completely abolish acceptor activity or greatly reduce it. The results suggest that the proteoglycan recognition consensus sequence for the attachment of glycosaminoglycans to core proteins consists of acidic amino acids closely followed by the tetrapeptide Ser-Gly-Xaa-Gly, where Xaa is any amino acid. The signal appears to be contained in the primary sequence information. In this regard it resembles a number of other signals for protein processing and intracellular routing.
Bourdon
M A
MA
Krusius
T
T
Campbell
S
S
Schwartz
N B
NB
Ruoslahti
E
E
D000595:Amino Acid Sequence; D000818:Animals; D002813:Chondrosarcoma / Q000201:enzymology; D006025:Glycosaminoglycans / Q000235:genetics / Q000378:metabolism*; D006681:HLA-D Antigens / Q000235:genetics; D006801:Humans; D007700:Kinetics; D010430:Pentosyltransferases / Q000378:metabolism; D011485:Protein Binding; D021382:Protein Sorting Signals / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D014994:Xylose / Q000378:metabolism; D000097608:UDP Xylose-Protein Xylosyltransferase
D006025:Glycosaminoglycans; D006681:HLA-D Antigens; D010430:Pentosyltransferases; D021382:Protein Sorting Signals; D011506:Proteins; D014994:Xylose; D000097608:UDP Xylose-Protein Xylosyltransferase