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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
A conserved interdomain interaction is a determinant of folding cooperativity in the GST fold
Biochemistry, Volume 50, No. 32, Year 2011
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Description
The canonical glutathione transferase (GST) fold found in many monomeric and dimeric proteins consists of two domains that differ in structure and conformational dynamics. However, no evidence exists that the two domains unfold/fold independently at equilibrium, indicating the significance of interdomain interactions in governing cooperativity between domains. Bioinformatics analyses indicate the interdomain interface of the GST fold is large, predominantly hydrophobic with a high packing density explaining cooperative interdomain behavior. Structural alignments reveal a topologically conserved lock-and-key interaction across the domain interface in which a bulky hydrophobic residue ("key") protrudes from the surface of the N-domain and inserts into a pocket ("lock") in the C-domain. To better understand the molecular basis for the contribution of interdomain interactions toward cooperativity within the GST fold in the absence of any influence from quaternary interactions, studies were done with two monomeric GST proteins: Escherichia coli Grx2 (EcGrx2) and human CLIC1 (hCLIC1). Replacing the methionine "key" residue with alanine is structurally nondisruptive, whereas it significantly diminishes the folding cooperativity of both proteins. The loss in cooperativity between domains in the mutants is reflected by a change in the equilibrium folding mechanism from a wild-type two-state process to a three-state process, populating a stable folding intermediate. © 2011 American Chemical Society.
Authors & Co-Authors
Parbhoo, Nishal
South Africa, Johannesburg
University of the Witwatersrand
Stoychev, Stoyan H.
South Africa, Johannesburg
University of the Witwatersrand
Fanucchi, Sylvia
South Africa, Johannesburg
University of the Witwatersrand
Achilonu, Ikechukwu Anthony
South Africa, Johannesburg
University of the Witwatersrand
Adamson, Roslin J.
South Africa, Johannesburg
University of the Witwatersrand
Fernandes, Manuel A.
South Africa, Johannesburg
University of the Witwatersrand
Gildenhuys, Samantha
South Africa, Johannesburg
University of the Witwatersrand
Dirr, Heini W.
South Africa, Johannesburg
University of the Witwatersrand
Statistics
Citations: 9
Authors: 8
Affiliations: 1
Identifiers
Doi:
10.1021/bi2006509
e-ISSN:
15204995