Structure-based design of an RNA-binding zinc finger.
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.
McColl
D J
DJ
Department of Biochemistry and Biophysics, University of California, 513 Parnassus Avenue, San Francisco, CA 94143-0448, USA.
Honchell
C D
CD
Frankel
A D
AD
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D015694:Gene Products, rev / Q000737:chemistry / Q000235:genetics; D015497:HIV-1; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D013329:Structure-Activity Relationship; D016335:Zinc Fingers / Q000235:genetics*; D054321:rev Gene Products, Human Immunodeficiency Virus
D015694:Gene Products, rev; D016601:RNA-Binding Proteins; D054321:rev Gene Products, Human Immunodeficiency Virus