Lela Vukovic, Hye Ran Koh, Sua Myong, and Klaus Schulten.
Substrate recognition and specificity of double-stranded RNA
binding proteins.
Biochemistry, 53:3457-3466, 2014.
(PMC: PMC4051425)
VUKO2014
Recognition of double-stranded (ds) RNA is an important part of many cellular pathways,
including RNA silencing, viral recognition, RNA editing, processing and transport. dsRNA
recognition is often achieved by dsRNA binding domains (dsRBDs). We use atomistic molecular
dynamics simulations to examine the binding interface of the transactivation response RNA
binding protein (TRBP) dsRBDs to dsRNA substrates. Our results explain the exclusive
selectivity of dsRBDs towards dsRNA and against DNA-RNA hybrid and dsDNA duplexes. We
also provide corresponding experimental evidence. The dsRNA duplex is recognized by
dsRBDs through the A-form of three duplex grooves and by the chemical properties of RNA
bases, which have 2'-hydroxyl groups on their sugar rings. Our simulations show that TRBP
dsRBD discriminates dsRNA from DNA-containing duplexes primarily through interactions at
two duplex grooves. The simulations also reveal that the conformation of the DNA-RNA
duplex can be modulated by dsRBD proteins, suggesting a potentially weak binding of dsRBDs
to DNA-RNA hybrids. Our study reveals the structural and molecular basis of protein-RNA
contact that gives rise to the substrate specificity of dsRNA binding proteins.
Download Full Text
The manuscripts available on our site are provided for your personal
use only and may not be retransmitted or redistributed without written
permissions from the paper's publisher and author. You may not upload any
of this site's material to any public server, on-line service, network, or
bulletin board without prior written permission from the publisher and
author. You may not make copies for any commercial purpose. Reproduction
or storage of materials retrieved from this web site is subject to the
U.S. Copyright Act of 1976, Title 17 U.S.C.
