Cited by 226Protein Structure and DynamicsGenomics and Chromatin DynamicsCRISPR and Genetic Engineering

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Structure-Based Design of Transcription Factors

Pomerantz, Joel L., Sharp, Phillip A., Pabo, Carl O.·1995·Science

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Abstract

Computer modeling suggested that transcription factors with novel sequence specificities could be designed by combining known DNA binding domains. This structure-based strategy was tested by construction of a fusion protein, ZFHD1, that contained zinc fingers 1 and 2 from Zif268, a short polypeptide linker, and the homeodomain from Oct-1. The fusion protein bound optimally to a sequence containing adjacent homeodomain (TAATTA) and zinc finger (NGGGNG) subsites. When fused to an activation domain, ZFHD1 regulated promoter activity in vivo in a sequence-specific manner. Analysis of known protein-DNA complexes suggests that many other DNA binding proteins could be designed in a similar fashion.

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Authors: Pomerantz, J. L., Sharp, P. A., & Pabo, C. O.
Affiliations: Harvard–MIT Division of Health Sciences and Technology (US)
Massachusetts Institute of Technology (US)
ORCID: Pomerantz, Joel L.
Sharp, Phillip A.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1995-01-06
Volume: 267
Issue: 5194
Pages: 93-96
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.7809612
OpenAlex: W2022704908
Cited by: 226
References: 18
Citations by year: 2025: 3 · 2024: 2 · 2023: 1 · 2022: 2 · 2019: 1 · 2018: 2 · 2017: 4 · 2015: 2 · 2014: 3 · 2013: 2 · 2012: 2
FWCI: 9.14
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Funders: National Cancer Institute (P01CA042063, P30CA014051)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
Keywords: structure-based protein design, DNA-binding domain, zinc finger, homeodomain, Zif268, Oct-1, fusion protein, sequence specificity, protein-DNA complex, promoter regulation, transactivation domain
MeSH terms: Amino Acid Sequence, Base Sequence, Binding Sites, Cloning, Molecular, Computer Simulation, DNA-Binding Proteins, Gene Expression Regulation, Models, Molecular, Molecular Sequence Data, Promoter Regions, Genetic, Recombinant Fusion Proteins, Transcription Factors, Transfection, Protein Engineering, Zinc Fingers, Homeodomain Proteins, Octamer Transcription Factor-1, Host Cell Factor C1

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