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Monomeric and dimeric bZIP transcription factor GCN4 bind at the same rate to their target DNA site.
Biochemistry. 2004 Jan 27; 43(3):718-27.B

Abstract

Basic leucine zipper (bZIP) transcription factors are dimeric proteins that recognize dyadic and mostly palindromic DNA sites. Dimerization of bZIP transcription factor GCN4 is linked to the folding of its C-terminal leucine zipper domain. However, monomeric GCN4, lacking a folded leucine zipper, also recognizes the DNA site with dimerization taking place on the DNA. Here we report the kinetics of DNA recognition by unfolded monomeric and folded dimeric derivatives of GCN4 using a 19 bp double-stranded DNA containing a palindromic CRE site. The rate of DNA binding of both monomeric and dimeric GCN4 has a bimolecular rate constant of 3-5 x 10(8) M(-1) s(-1), which is near the diffusion limit. Because the rate of dimerization of GCN4 is slower (1.7 x 10(7) M(-1) s(-1)) than the rate of DNA association, the formation of the dimeric GCN4-DNA complex through consecutive binding of two monomers (monomer pathway) is faster when starting from free monomers. Thus, the results presented here support facilitated and rapid target recognition by the monomeric transcription factor. However, DNA binding of preformed folded dimeric GCN4 is as rapid as complex formation through the monomer pathway. Therefore, the monomer and dimer pathways are kinetically equivalent if monomeric and dimeric GCN4 are at equilibrium. Hence, the dimer pathway may also have a role under in vivo conditions. The lower affinity of GCN4 in which two DNA contacting residues have been mutated is due exclusively to the faster dissociation of the mutant protein-DNA complex and not to slower complex formation.

Authors+Show Affiliations

Biochemisches Institut der Universität Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14730976

Citation

Cranz, Susanne, et al. "Monomeric and Dimeric bZIP Transcription Factor GCN4 Bind at the Same Rate to Their Target DNA Site." Biochemistry, vol. 43, no. 3, 2004, pp. 718-27.
Cranz S, Berger C, Baici A, et al. Monomeric and dimeric bZIP transcription factor GCN4 bind at the same rate to their target DNA site. Biochemistry. 2004;43(3):718-27.
Cranz, S., Berger, C., Baici, A., Jelesarov, I., & Bosshard, H. R. (2004). Monomeric and dimeric bZIP transcription factor GCN4 bind at the same rate to their target DNA site. Biochemistry, 43(3), 718-27.
Cranz S, et al. Monomeric and Dimeric bZIP Transcription Factor GCN4 Bind at the Same Rate to Their Target DNA Site. Biochemistry. 2004 Jan 27;43(3):718-27. PubMed PMID: 14730976.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Monomeric and dimeric bZIP transcription factor GCN4 bind at the same rate to their target DNA site. AU - Cranz,Susanne, AU - Berger,Christine, AU - Baici,Antonio, AU - Jelesarov,Ilian, AU - Bosshard,Hans Rudolf, PY - 2004/1/21/pubmed PY - 2004/5/20/medline PY - 2004/1/21/entrez SP - 718 EP - 27 JF - Biochemistry JO - Biochemistry VL - 43 IS - 3 N2 - Basic leucine zipper (bZIP) transcription factors are dimeric proteins that recognize dyadic and mostly palindromic DNA sites. Dimerization of bZIP transcription factor GCN4 is linked to the folding of its C-terminal leucine zipper domain. However, monomeric GCN4, lacking a folded leucine zipper, also recognizes the DNA site with dimerization taking place on the DNA. Here we report the kinetics of DNA recognition by unfolded monomeric and folded dimeric derivatives of GCN4 using a 19 bp double-stranded DNA containing a palindromic CRE site. The rate of DNA binding of both monomeric and dimeric GCN4 has a bimolecular rate constant of 3-5 x 10(8) M(-1) s(-1), which is near the diffusion limit. Because the rate of dimerization of GCN4 is slower (1.7 x 10(7) M(-1) s(-1)) than the rate of DNA association, the formation of the dimeric GCN4-DNA complex through consecutive binding of two monomers (monomer pathway) is faster when starting from free monomers. Thus, the results presented here support facilitated and rapid target recognition by the monomeric transcription factor. However, DNA binding of preformed folded dimeric GCN4 is as rapid as complex formation through the monomer pathway. Therefore, the monomer and dimer pathways are kinetically equivalent if monomeric and dimeric GCN4 are at equilibrium. Hence, the dimer pathway may also have a role under in vivo conditions. The lower affinity of GCN4 in which two DNA contacting residues have been mutated is due exclusively to the faster dissociation of the mutant protein-DNA complex and not to slower complex formation. SN - 0006-2960 UR - https://www.unboundmedicine.com/medline/citation/14730976/Monomeric_and_dimeric_bZIP_transcription_factor_GCN4_bind_at_the_same_rate_to_their_target_DNA_site_ DB - PRIME DP - Unbound Medicine ER -