Long-range interactions within a nonnative protein

Judith Klein-Seetharaman, Maki Oikawa, Shaun B. Grimshaw, Julia Wirmer, Elke Duchardt, Tadashi Ueda, Taiji Imoto, Lorna J. Smith, Christopher M. Dobson, Harald Schwalbe

Research output: Contribution to journalArticle

511 Citations (Scopus)

Abstract

Protein folding and unfolding are coupled to a range of biological phenomena, from the regulation of cellular activity to the onset of neurodegenerative diseases. Defining the nature of the conformations sampled in nonnative proteins is crucial for understanding the origins of such phenomena. We have used a combination of nuclear magnetic resonance (NMR) spectroscopy and site-directed mutagenesis to study unfolded states of the protein lysozyme. Extensive clusters of hydrophobic structure exist within the wild-type protein even under strongly denaturing conditions. These clusters involve distinct regions of the sequence but are all disrupted by a single point mutation that replaced residue Trp62 with Gly located at the interface of the two major structural domains in the native state. Thus, nativetike structure in the denatured protein is stabilized by the involvement of Trp62 in nonnative and long-range interactions.

Original languageEnglish
Pages (from-to)1719-1722
Number of pages4
JournalScience
Volume295
Issue number5560
DOIs
Publication statusPublished - Mar 1 2002

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Protein Unfolding
Biological Phenomena
Proteins
Protein Folding
Muramidase
Site-Directed Mutagenesis
Point Mutation
Neurodegenerative Diseases
Magnetic Resonance Spectroscopy

All Science Journal Classification (ASJC) codes

  • General

Cite this

Klein-Seetharaman, J., Oikawa, M., Grimshaw, S. B., Wirmer, J., Duchardt, E., Ueda, T., ... Schwalbe, H. (2002). Long-range interactions within a nonnative protein. Science, 295(5560), 1719-1722. https://doi.org/10.1126/science.1067680

Long-range interactions within a nonnative protein. / Klein-Seetharaman, Judith; Oikawa, Maki; Grimshaw, Shaun B.; Wirmer, Julia; Duchardt, Elke; Ueda, Tadashi; Imoto, Taiji; Smith, Lorna J.; Dobson, Christopher M.; Schwalbe, Harald.

In: Science, Vol. 295, No. 5560, 01.03.2002, p. 1719-1722.

Research output: Contribution to journalArticle

Klein-Seetharaman, J, Oikawa, M, Grimshaw, SB, Wirmer, J, Duchardt, E, Ueda, T, Imoto, T, Smith, LJ, Dobson, CM & Schwalbe, H 2002, 'Long-range interactions within a nonnative protein', Science, vol. 295, no. 5560, pp. 1719-1722. https://doi.org/10.1126/science.1067680
Klein-Seetharaman J, Oikawa M, Grimshaw SB, Wirmer J, Duchardt E, Ueda T et al. Long-range interactions within a nonnative protein. Science. 2002 Mar 1;295(5560):1719-1722. https://doi.org/10.1126/science.1067680
Klein-Seetharaman, Judith ; Oikawa, Maki ; Grimshaw, Shaun B. ; Wirmer, Julia ; Duchardt, Elke ; Ueda, Tadashi ; Imoto, Taiji ; Smith, Lorna J. ; Dobson, Christopher M. ; Schwalbe, Harald. / Long-range interactions within a nonnative protein. In: Science. 2002 ; Vol. 295, No. 5560. pp. 1719-1722.
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