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Designed Arginine-Rich RNA-Binding Peptides with Picomolar Affinity

Austin, Ryan J. and Xia, Tianbing and Ren, Jinsong and Takahashi, Terry T. and Roberts, Richard W. (2002) Designed Arginine-Rich RNA-Binding Peptides with Picomolar Affinity. Journal of the American Chemical Society, 124 (37). pp. 10966-10967. ISSN 0002-7863. doi:10.1021/ja026610b. https://resolver.caltech.edu/CaltechAUTHORS:20170414-101608459

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Abstract

Arginine-rich peptide motifs (ARMs) capable of binding unique RNA structures play critical roles in transcription, translation, RNA trafficking, and RNA packaging. Bacteriophage ARMs necessary for transcription antitermination bind to distinct boxB RNA hairpin sequences with a characteristic induced α-helical structure. Characterization of ARMs from lambdoid phages reveals that the dissociation constant of the P22 bacteriophage model−antitermination complex (P22_(N21)−P22boxB) is 200 ± 56 pM in free solution at physiologic concentrations of monovalent cation, significantly stronger than previously determined by gel mobility shift and polyacrylamide gel coelectophoresis, and 2 orders of magnitude stronger than the tightest known native ARM−RNA interaction at physiological salt. Here, we use a reciprocal design approach to enhance the binding affinity of two separate α-helical ARM−RNA interactions; one derived from the native λ phage antitermination complex and a second isolated using mRNA display selection experiments targeting boxB RNA.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/ja026610bDOIArticle
http://pubs.acs.org/doi/full/10.1021/ja026610bPublisherArticle
http://pubs.acs.org/doi/suppl/10.1021/ja026610bPublisherSupporting Information
ORCID:
AuthorORCID
Austin, Ryan J.0000-0002-5302-5266
Roberts, Richard W.0000-0002-8587-5097
Additional Information:© 2002 American Chemical Society. Received 19 April 2002. Published online 22 August 2002. Published in print 1 September 2002. We thank Dr. Adam Frankel for his comments on the manuscript. This work was supported by a NSF Grant 9876246 (R.W.R), NIH Grant GM60416 (R.W.R), and training grant T32 GM08501.
Funders:
Funding AgencyGrant Number
NSF9876246
NIHGM60416
NIH Predoctoral FellowshipT32 GM08501
Issue or Number:37
DOI:10.1021/ja026610b
Record Number:CaltechAUTHORS:20170414-101608459
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170414-101608459
Official Citation:Designed Arginine-Rich RNA-Binding Peptides with Picomolar Affinity Ryan J. Austin, Tianbing Xia, Jinsong Ren, Terry T. Takahashi, and Richard W. Roberts Journal of the American Chemical Society 2002 124 (37), 10966-10967 DOI: 10.1021/ja026610b
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:76569
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:14 Apr 2017 18:14
Last Modified:15 Nov 2021 17:01

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