Toggle Main Menu Toggle Search

Open Access padlockePrints

Structural Analysis of the Recognition of the Negative Regulator NmrA and DNA by the Zinc Finger from the GATA-Type Transcription Factor AreA

Lookup NU author(s): Dr Heather Lamb, Professor Alastair Hawkins


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Amongst the most common protein motifs in eukaryotes are zinc fingers (ZFs), which, although largely known as DNA binding modules, also can have additional important regulatory roles in forming protein:protein interactions. AreA is a transcriptional activator central to nitrogen metabolism in Aspergillus nidulans. AreA contains a GATA-type ZF that has a competing dual recognition function, binding either DNA or the negative regulator NmrA. We report the crystal structures of three AreA ZF-NmrA complexes including two with bound NAD+ or NADP+. The molecular recognition of AreA ZF-NmrA involves binding of the ZF to NmrA via hydrophobic and hydrogen bonding interactions through helices α1, α6 and α11. Comparison with an earlier NMR solution structure of AreA ZF-DNA complex by overlap of the AreA ZFs shows that parts of helices α6 and α11 of NmrA are positioned close to the GATA motif of the DNA, mimicking the major groove of DNA. The extensive overlap of DNA with NmrA explains their mutually exclusive binding to the AreA ZF. The presence of bound NAD+/NADP+ in the NmrA-AreaA ZF complex, however, causes minimal structural changes. Thus, any regulatory effects on AreA function mediated by the binding of oxidised nicotinamide dinucleotides to NmrA in the NmrA-AreA ZF complex appear not to be modulated via protein conformational rearrangements. © 2008 Elsevier Ltd. All rights reserved.

Publication metadata

Author(s): Kotaka M, Johnson C, Lamb HK, Hawkins AR, Ren J, Stammers DK

Publication type: Article

Publication status: Published

Journal: Journal of Molecular Biology

Year: 2008

Volume: 381

Issue: 2

Pages: 373-382

ISSN (print): 0022-2836

ISSN (electronic): 1089-8638

Publisher: Academic Press


DOI: 10.1016/j.jmb.2008.05.077


Altmetrics provided by Altmetric