A motif unique to the human DEAD-box protein DDX3 is important for nucleic acid binding, ATP hydrolysis, RNA/DNA unwinding and HIV-1 replication
- DEAD-box proteins are enzymes endowed with nucleic acid-dependent ATPase, RNA translocase and unwinding activities. The human DEAD-box protein DDX3 has been shown to play important roles in tumor proliferation and viral infections. In particular, DDX3 has been identified as an essential cofactor for HIV-1 replication. Here we characterized a set of DDX3 mutants biochemically with respect to nucleic acid binding, ATPase and helicase activity. In particular, we addressed the functional role of a unique insertion between motifs I and Ia of DDX3 and provide evidence for its implication in nucleic acid binding and HIV-1 replication. We show that human DDX3 lacking this domain binds HIV-1 RNA with lower affinity. Furthermore, a specific peptide ligand for this insertion selected by phage display interferes with HIV-1 replication after transduction into HelaP4 cells. Besides broadening our understanding of the structure-function relationships of this important protein, our results identify a specific domain of DDX3 which may be suited as target for antiviral drugs designed to inhibit cellular cofactors for HIV-1 replication.
Author: | Anna Garbelli, Sandra BeermannGND, Giulia Di Cicco, Ursula Dietrich, Giovanni Maga |
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URN: | urn:nbn:de:hebis:30-114206 |
DOI: | https://doi.org/10.1371/journal.pone.0019810 |
ISSN: | 1932-6203 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/21589879 |
Parent Title (English): | PLoS One |
Publisher: | PLoS |
Place of publication: | Lawrence, Kan. |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2011/05/12 |
Date of first Publication: | 2011/05/12 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2011/09/01 |
Volume: | 6 |
Issue: | (5): e19810 |
Page Number: | 15 |
First Page: | 1 |
Last Page: | 15 |
Note: | Copyright: © 2011 Garbelli et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
HeBIS-PPN: | 27511421X |
Institutes: | Angeschlossene und kooperierende Institutionen / Georg-Speyer-Haus |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Sammlungen: | Universitätspublikationen |
Sammlung Biologie / Sondersammelgebiets-Volltexte | |
Licence (German): | Creative Commons - Namensnennung 3.0 |