Adaptability at the protein-DNA interface is an important aspect of sequence recognition by bZIP proteins

Joon Kim, Dimitris Tzamarias, Thomas Ellenberger, Stephen C. Harrison, Kevin Struhl

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

The related AP-1 and ATF/CREB families of transcriptional regulatory proteins bind as dimers to overlapping or adjacent DNA half-sites by using a bZIP structural motif. Using genetic selections, we isolate derivatives of yeast GCN4 that affect DNA-binding specificity at particular positions of the AP-1 target sequence. In general, altered DNA-binding specificity results from the substitution of larger hydrophobic amino acids for GCN4 residues that contact base pairs. However, in several cases, DNA binding by the mutant proteins cannot be simply explained in terms of the GCN4-AP-1 structure; movement of the protein and/or DNA structural changes are required to accommodate the amino acid substitutions. The quintet of GCN4 residues that make base-pair contacts do not entirely determine DNA-binding specificity because these residues are highly conserved in the bZIP family, yet many of the bZIP proteins bind to distinct DNA sites. The α-helical fork between the GCN4 DNA-binding and dimerization surfaces is important for half-site spacing preferences, because mutations in the fork alter the relative affinity for AP-1 and ATF/CREB sites. The basic region in the protein-DNA complex is a long isolated α-helix, with no constraints from other parts of a folded domain. From all of these considerations, we suggest that small shifts in position and orientation or local deformations in the α-helical backbone distinguish one bZIP complex from another.

Original languageEnglish
Pages (from-to)4513-4517
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number10
Publication statusPublished - 1993 May 15
Externally publishedYes

Fingerprint

Basic-Leucine Zipper Transcription Factors
DNA
Transcription Factor AP-1
Proteins
Base Pairing
Genetic Selection
DNA-Binding Proteins
Dimerization
Mutant Proteins
Amino Acid Substitution
Yeasts
Amino Acids
Mutation

Keywords

  • DNA-binding protein
  • Gene regulation
  • Leucine zipper
  • Transcription factor
  • Yeast GCN4

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Adaptability at the protein-DNA interface is an important aspect of sequence recognition by bZIP proteins. / Kim, Joon; Tzamarias, Dimitris; Ellenberger, Thomas; Harrison, Stephen C.; Struhl, Kevin.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 90, No. 10, 15.05.1993, p. 4513-4517.

Research output: Contribution to journalArticle

Kim, Joon ; Tzamarias, Dimitris ; Ellenberger, Thomas ; Harrison, Stephen C. ; Struhl, Kevin. / Adaptability at the protein-DNA interface is an important aspect of sequence recognition by bZIP proteins. In: Proceedings of the National Academy of Sciences of the United States of America. 1993 ; Vol. 90, No. 10. pp. 4513-4517.
@article{dac3a567aacf45deba38b74b8ecf8605,
title = "Adaptability at the protein-DNA interface is an important aspect of sequence recognition by bZIP proteins",
abstract = "The related AP-1 and ATF/CREB families of transcriptional regulatory proteins bind as dimers to overlapping or adjacent DNA half-sites by using a bZIP structural motif. Using genetic selections, we isolate derivatives of yeast GCN4 that affect DNA-binding specificity at particular positions of the AP-1 target sequence. In general, altered DNA-binding specificity results from the substitution of larger hydrophobic amino acids for GCN4 residues that contact base pairs. However, in several cases, DNA binding by the mutant proteins cannot be simply explained in terms of the GCN4-AP-1 structure; movement of the protein and/or DNA structural changes are required to accommodate the amino acid substitutions. The quintet of GCN4 residues that make base-pair contacts do not entirely determine DNA-binding specificity because these residues are highly conserved in the bZIP family, yet many of the bZIP proteins bind to distinct DNA sites. The α-helical fork between the GCN4 DNA-binding and dimerization surfaces is important for half-site spacing preferences, because mutations in the fork alter the relative affinity for AP-1 and ATF/CREB sites. The basic region in the protein-DNA complex is a long isolated α-helix, with no constraints from other parts of a folded domain. From all of these considerations, we suggest that small shifts in position and orientation or local deformations in the α-helical backbone distinguish one bZIP complex from another.",
keywords = "DNA-binding protein, Gene regulation, Leucine zipper, Transcription factor, Yeast GCN4",
author = "Joon Kim and Dimitris Tzamarias and Thomas Ellenberger and Harrison, {Stephen C.} and Kevin Struhl",
year = "1993",
month = "5",
day = "15",
language = "English",
volume = "90",
pages = "4513--4517",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "10",

}

TY - JOUR

T1 - Adaptability at the protein-DNA interface is an important aspect of sequence recognition by bZIP proteins

AU - Kim, Joon

AU - Tzamarias, Dimitris

AU - Ellenberger, Thomas

AU - Harrison, Stephen C.

AU - Struhl, Kevin

PY - 1993/5/15

Y1 - 1993/5/15

N2 - The related AP-1 and ATF/CREB families of transcriptional regulatory proteins bind as dimers to overlapping or adjacent DNA half-sites by using a bZIP structural motif. Using genetic selections, we isolate derivatives of yeast GCN4 that affect DNA-binding specificity at particular positions of the AP-1 target sequence. In general, altered DNA-binding specificity results from the substitution of larger hydrophobic amino acids for GCN4 residues that contact base pairs. However, in several cases, DNA binding by the mutant proteins cannot be simply explained in terms of the GCN4-AP-1 structure; movement of the protein and/or DNA structural changes are required to accommodate the amino acid substitutions. The quintet of GCN4 residues that make base-pair contacts do not entirely determine DNA-binding specificity because these residues are highly conserved in the bZIP family, yet many of the bZIP proteins bind to distinct DNA sites. The α-helical fork between the GCN4 DNA-binding and dimerization surfaces is important for half-site spacing preferences, because mutations in the fork alter the relative affinity for AP-1 and ATF/CREB sites. The basic region in the protein-DNA complex is a long isolated α-helix, with no constraints from other parts of a folded domain. From all of these considerations, we suggest that small shifts in position and orientation or local deformations in the α-helical backbone distinguish one bZIP complex from another.

AB - The related AP-1 and ATF/CREB families of transcriptional regulatory proteins bind as dimers to overlapping or adjacent DNA half-sites by using a bZIP structural motif. Using genetic selections, we isolate derivatives of yeast GCN4 that affect DNA-binding specificity at particular positions of the AP-1 target sequence. In general, altered DNA-binding specificity results from the substitution of larger hydrophobic amino acids for GCN4 residues that contact base pairs. However, in several cases, DNA binding by the mutant proteins cannot be simply explained in terms of the GCN4-AP-1 structure; movement of the protein and/or DNA structural changes are required to accommodate the amino acid substitutions. The quintet of GCN4 residues that make base-pair contacts do not entirely determine DNA-binding specificity because these residues are highly conserved in the bZIP family, yet many of the bZIP proteins bind to distinct DNA sites. The α-helical fork between the GCN4 DNA-binding and dimerization surfaces is important for half-site spacing preferences, because mutations in the fork alter the relative affinity for AP-1 and ATF/CREB sites. The basic region in the protein-DNA complex is a long isolated α-helix, with no constraints from other parts of a folded domain. From all of these considerations, we suggest that small shifts in position and orientation or local deformations in the α-helical backbone distinguish one bZIP complex from another.

KW - DNA-binding protein

KW - Gene regulation

KW - Leucine zipper

KW - Transcription factor

KW - Yeast GCN4

UR - http://www.scopus.com/inward/record.url?scp=0027310483&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027310483&partnerID=8YFLogxK

M3 - Article

C2 - 8506292

AN - SCOPUS:0027310483

VL - 90

SP - 4513

EP - 4517

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 10

ER -