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An engineered leucine zipper a position mutant with an unusual three-state unfolding pathway
Journal article   Open access   Peer reviewed

An engineered leucine zipper a position mutant with an unusual three-state unfolding pathway

Hai Zhu, Scott A. Celinski, J. Martin Scholtz and James C. Hu
Protein science, Vol.10(1), pp.24-33
01/01/2001
DOI: 10.1110/ps.30901
PMCID: PMC2249852
PMID: 11266591
url
https://europepmc.org/articles/pmc2249852View
Published (Version of record) Open Access

Abstract

The leucine zipper is a dimeric coiled-coil structural motif consisting of four to six heptad repeats, designated ( abcdefg ) n . In the GCN4 leucine zipper, a position 16 in the third heptad is occupied by an Asn residue whereas the other a positions are Val residues. Recently, we have constructed variants of the GCN4 leucine zipper in which the a position Val residues were replaced by Ile. The folding and unfolding of the wild-type GCN4 leucine zipper and the Val to Ile variant both adhere to a simple two-state mechanism. In this study, another variant of the GCN4 leucine zipper was constructed by moving the single Asn residue from a position 16 to a position 9. This switch causes the thermal unfolding of the GCN4 leucine zipper to become three state. The unfolding pathway of this variant was determined by thermal denaturation, limited proteinase K digestion, and sedimentation equilibrium analysis. Our data are consistent with a model in which the variant first unfolds from its N terminus and changes the oligomerization specificity from a native dimer to a partially unfolded intermediate containing a mixture of dimers and trimers and then completely unfolds to unstructured monomers.
folding intermediate Leucine zippers protein folding three-state unfolding

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