TY - JOUR
T1 - The proteoglycan bikunin has a defined sequence
AU - Ly, Mellisa
AU - Leach, Franklin E.
AU - Laremore, Tatiana N.
AU - Toida, Toshihiko
AU - Amster, I. Jonathan
AU - Linhardt, Robert J.
N1 - Funding Information:
The authors thank D. Zagorevski for his expertise in the proteomics core at Rensselaer Polytechnic Institute and the US National Institutes of Health for support (GM38060).
PY - 2011/11
Y1 - 2011/11
N2 - Proteoglycans are complex glycoconjugates that regulate critical biological pathways in all higher organisms. Bikunin, the simplest proteoglycan, with a single glycosaminoglycan chain, is a serine protease inhibitor used to treat acute pancreatitis. Unlike nucleic acids and proteins, whose synthesis is template driven, Golgi-synthesized glycosaminoglycans are not believed to have predictable or deterministic sequences. Bikunin peptidoglycosaminoglycans were prepared and fractionated to obtain a collection of size-similar and charge-similar chains. Fourier transform mass spectral analysis identified a small number of parent molecular ions corresponding to monocompositional peptidoglycosaminoglycans. Fragmentation using collision-induced dissociation unexpectedly afforded a single sequence for each monocompositional parent ion, unequivocally demonstrating the presence of a defined sequence. The biosynthetic pathway common to all proteoglycans suggests that even more structurally complex proteoglycans, such as heparan sulfate, may have defined sequences, requiring a readjustment in the understanding of information storage in complex glycans.
AB - Proteoglycans are complex glycoconjugates that regulate critical biological pathways in all higher organisms. Bikunin, the simplest proteoglycan, with a single glycosaminoglycan chain, is a serine protease inhibitor used to treat acute pancreatitis. Unlike nucleic acids and proteins, whose synthesis is template driven, Golgi-synthesized glycosaminoglycans are not believed to have predictable or deterministic sequences. Bikunin peptidoglycosaminoglycans were prepared and fractionated to obtain a collection of size-similar and charge-similar chains. Fourier transform mass spectral analysis identified a small number of parent molecular ions corresponding to monocompositional peptidoglycosaminoglycans. Fragmentation using collision-induced dissociation unexpectedly afforded a single sequence for each monocompositional parent ion, unequivocally demonstrating the presence of a defined sequence. The biosynthetic pathway common to all proteoglycans suggests that even more structurally complex proteoglycans, such as heparan sulfate, may have defined sequences, requiring a readjustment in the understanding of information storage in complex glycans.
UR - http://www.scopus.com/inward/record.url?scp=80054871765&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80054871765&partnerID=8YFLogxK
U2 - 10.1038/nchembio.673
DO - 10.1038/nchembio.673
M3 - Article
C2 - 21983600
AN - SCOPUS:80054871765
SN - 1552-4450
VL - 7
SP - 827
EP - 833
JO - Nature Chemical Biology
JF - Nature Chemical Biology
IS - 11
ER -