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PMID: 10449725 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Structure-based design of an RNA-binding zinc finger.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 96 ·No. 17 ·1999-08-17 ·Pages 9521-6

McColl DJ, Honchell CD, Frankel AD

Abstract

A structure-based approach was used to design RNA-binding zinc fingers that recognize the HIV-1 Rev response element (RRE). An arginine-rich alpha-helix from HIV-1 Rev was engineered into the zinc finger framework, and the designed fingers were shown to bind specifically to the RRE with high affinity and in a zinc-dependent manner, and display cobalt absorption and CD spectra characteristic of properly folded fingers. The results indicate that a monomeric zinc finger can recognize a specific nucleic acid site and that the alpha-helix of a finger can be used to recognize the major groove of RNA as well as DNA. The RRE-binding zinc fingers demonstrate how structure-based approaches may be used in the design of potential RNA-binding therapeutics and provide a framework for selecting RNA-binding fingers with desired specifications.

MeSH Terms
Amino Acid Sequence Circular Dichroism Gene Products, rev/chemistry,genetics HIV-1 Models, Molecular Molecular Sequence Data Protein Conformation Protein Folding RNA-Binding Proteins/chemistry,genetics Structure-Activity Relationship Zinc Fingers/genetics rev Gene Products, Human Immunodeficiency Virus
Chemicals
Gene Products, rev RNA-Binding Proteins rev Gene Products, Human Immunodeficiency Virus
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
McColl D J
Department of Biochemistry and Biophysics, University of California, 513 Parnassus Avenue, San Francisco, CA 94143-0448, USA.
Honchell C D
Frankel A D
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.96.17.9521
Published
1999-08-17
Pages
9521-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC22241
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.96.17.9521 PMC Full Text View journal details
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