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Structure-based Design of an RNA-binding Zinc Finger

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Specialty Science
Date 1999 Aug 18
PMID 10449725
Citations 20
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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.

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References
1.
Miller J, McLachlan A, Klug A . Repetitive zinc-binding domains in the protein transcription factor IIIA from Xenopus oocytes. EMBO J. 1985; 4(6):1609-14. PMC: 554390. DOI: 10.1002/j.1460-2075.1985.tb03825.x. View

2.
FRIESEN W, Darby M . Specific RNA binding proteins constructed from zinc fingers. Nat Struct Biol. 1998; 5(7):543-6. DOI: 10.1038/794. View

3.
Parraga G, Horvath S, Eisen A, TAYLOR W, Hood L, Young E . Zinc-dependent structure of a single-finger domain of yeast ADR1. Science. 1988; 241(4872):1489-92. DOI: 10.1126/science.3047872. View

4.
Lee M, Gippert G, Soman K, Case D, Wright P . Three-dimensional solution structure of a single zinc finger DNA-binding domain. Science. 1989; 245(4918):635-7. DOI: 10.1126/science.2503871. View

5.
Joho K, Darby M, Crawford E, Brown D . A finger protein structurally similar to TFIIIA that binds exclusively to 5S RNA in Xenopus. Cell. 1990; 61(2):293-300. DOI: 10.1016/0092-8674(90)90809-s. View