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Structure of an intermediate in the unfolding of creatine kinase
Author(s) -
Webb Timothy I.,
Morris Glenn E.
Publication year - 2000
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/1097-0134(20010201)42:2<269::aid-prot140>3.0.co;2-y
Subject(s) - guanidinium chloride , creatine kinase , chemistry , monomer , gene isoform , protease , epitope , dissociation (chemistry) , biophysics , protein subunit , crystallography , biochemistry , protein structure , enzyme , antibody , biology , organic chemistry , immunology , gene , polymer
The homodimeric muscle isoform of creatine kinase (MM‐CK) unfolds on exposure to low levels of guanidinium chloride (GdmCl) to yield a partly folded monomeric intermediate. Those regions of MM‐CK that experience local unfolding were previously identified through an extensive study of antibody accessibility and protease sensitivity. Since these studies were completed, the coordinates of the rabbit isoform (MM‐CK) were released. In light of this, we have determined the minimum changes to this structure required to explain our data on protease and epitope accessibility in the intermediate. We propose that the observed changes occur through (a) disruption of the monomer‐monomer interface during dissociation, (b) separation and/ or unfolding of domains or subdomains, and (c) the partial unfolding of solvent‐exposed helices. The proposed structure for the intermediate is consistent both with current models of unfolding intermediates and the results of independent studies pertaining to the unfolding of creatine kinase. Proteins 2001;42:269–278. © 2000 Wiley‐Liss, Inc.