The proteoglycan bikunin has a defined sequence

Mellisa Ly, Franklin E. Leach, Tatiana N. Laremore, Toshihiko Toida, I. Jonathan Amster, Robert J. Linhardt

Research output: Contribution to journalArticlepeer-review

128 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)827-833
Number of pages7
JournalNature Chemical Biology
Volume7
Issue number11
DOIs
StatePublished - Nov 2011

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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