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The role of helix stabilizing residues in GCN4 basic region folding and DNA binding
Author(s) -
Hollenbeck Jessica J.,
McClain Diana L.,
Oakley Martha G.
Publication year - 2002
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.0211102
Subject(s) - leucine zipper , bzip domain , coiled coil , dna , hmg box , dna binding domain , biophysics , dna binding protein , helix (gastropod) , chemistry , binding site , basic helix loop helix leucine zipper transcription factors , protein structure , zipper , crystallography , biochemistry , biology , transcription factor , ecology , algorithm , snail , computer science , gene
Basic region leucine zipper (bZip) proteins contain a bipartite DNA‐binding motif consisting of a coiled‐coil leucine zipper dimerization domain and a highly charged basic region that directly contacts DNA. The basic region is largely unfolded in the absence of DNA, but adopts a helical conformation upon DNA binding. Although a coil → helix transition is entropically unfavorable, this conformational change positions the DNA‐binding residues appropriately for sequence‐specific interactions with DNA. The N‐terminal residues of the GCN4 DNA‐binding domain, DPAAL, make no DNA contacts and are not part of the conserved basic region, but are nonetheless important for DNA binding. Asp and Pro are often found at the N‐termini of α‐helices, and such N‐capping motifs can stabilize α‐helical structure. In the present study, we investigate whether these two residues serve to stabilize a helical conformation in the GCN4 basic region, lowering the energetic cost for DNA binding. Our results suggest that the presence of these residues contributes significantly to helical structure and to the DNA‐binding ability of the basic region in the absence of the leucine zipper. Similar helix‐capping motifs are found in approximately half of all bZip domains, and the implications of these findings for in vivo protein function are discussed.