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Bioinformatics Advance Access published online on September 11, 2006

Bioinformatics, doi:10.1093/bioinformatics/btl470
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© 2006 The Author(s)
Received June 26, 2006
Revised August 31, 2006
Accepted August 31, 2006

Article

Protein-RNA interactions: exploring binding patterns with a three-dimensional superposition analysis of high resolution structures

N. Morozova 1 1, J. Allers 2 1, J. Myers 2, and Y. Shamoo 2 *

1 current address: Harvard School of Public Health, Boston, MA
2 Department of Biochemistry and Cell Biology, Rice University, 6100 Main Street, Houston, TX, 77005

* To whom correspondence should be addressed.
Y. Shamoo, E-mail: shamoo{at}rice.edu


   Abstract

Motivation: The recognition of specific RNA sequences and structures by proteins is critical to our understanding of RNA processing, gene expression and viral replication. The diversity of RNA structures suggests that RNA recognition is substantially different than that of DNA.

Results: The atomic coordinates of 41 protein-RNA complexes have been used to probe composite nucleoside binding pockets that form the structural and chemical underpinnings of base recognition. Composite nucleoside binding pockets were constructed using three dimensional superpositions of each RNA nucleoside. Unlike protein-DNA interactions which are dominated by accessibility, RNA recognition frequently occurs in non-canonical and single-strand-like structures that allow interactions to occur from a much wider set of geometries and make fuller use of unique base shapes and hydrogen-bonding ability. By constructing composites that include all van der Waals, hydrogen bonding, stacking and general non-polar interactions made to a particular nucleoside, the strategies employed are made readily visible. Protein-RNA interactions can result in the formation of a glove-like tight binding pocket around RNA bases, but the size, shape and non-polar binding patterns differ between specific RNA bases. We show that adenine can be distinguished from guanine based on the size and shape of the binding pocket and steric exclusion of the guanine N2 exocyclic amino group. The unique shape and hydrogen bonding pattern for each RNA base allow proteins to make specific interactions through a very small number of contacts, as few as two in some cases.

Availability: The program ENTANGLE is available from http://www.bioc.rice.edu/~shamoo.


Associate Editor: Anna Tramontano

1 Both authors contributed equally to this work


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