Direct NMR measurement of the folding kinetics of a trimeric peptide

Xiaoyan Liu, Donald L. Siegel, Pei Fan, Barbara Brodsky, Jean Baum

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Direct NMR measurements of the folding kinetics are performed on a collagen-like triple helical peptide. The triple helical peptide was designed to model a biologically important region of collagen and has the sequence (POG)3ITGARGLAG(POG)4. Triple helical peptides were synthesized with specifically labeled 15N amino acid residues in key positions, and the kinetics of folding of the individual residues were monitored directly by measuring the loss of monomer intensity and the increase in trimer intensity. The residues at the terminal ends and central region could be followed independently and quantitated directly. Residues located at the terminal ends have rates and kinetics of folding that are distinct from residues in the central region of the peptide. This allows the monitoring of different steps in the folding mechanism and the postulation of the existence of a kinetic intermediate. The NMR data are consistent with a mechanism of association/nucleation and propagation. Hereditary connective tissue diseases are associated with mutations that result in abnormal folding of collagen, and the NMR folding experiments on a collagen-like peptide provide a basis for characterizing the molecular defect in folding mutations.

Original languageEnglish (US)
Pages (from-to)4306-4313
Number of pages8
JournalBiochemistry
Volume35
Issue number14
DOIs
StatePublished - Apr 9 1996

All Science Journal Classification (ASJC) codes

  • Biochemistry

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