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 journalArticlepeer-review

570 Scopus citations


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 (US)
Pages (from-to)1719-1722
Number of pages4
Issue number5560
StatePublished - Mar 1 2002
Externally publishedYes

ASJC Scopus subject areas

  • General


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