Year: 2018
Type: article
Abstract: RNA polymerase (RNAP) secondary-channel binding proteins have similar structures and directly bind to RNAP itself, unlike many transcriptional factors that instead interact with DNA. Since these proteins have different functions yet bind to the same site on RNAP, competition for binding determines the ensuing regulatory effects (1⇓⇓⇓–5). In PNAS, Kim et al. (6) report a posttranslational regulation of Salmonella DksA mediated by DnaJ. Under oxidative stress, two pairs of cysteine disulfides within the DksA zinc-finger region are known to result in substantial structural changes in this protein (7). This DksAoxi state is now reported to be reversed and reduced by DnaJ to DksAred (6). Such posttranslational regulation of DksA seems to add another wrinkle to the many puzzling regulatory properties of RNAP secondary-channel proteins (Fig. 1).
Fig. 1.
Structural modifications of DksA by pH (19) or oxidation (6, 7) that may change its ability to bind RNAP. The presence of DksA2 depends on the presence of Zn in the media (17, 18). (p)ppGpp binding sites are labeled with red stars (11⇓⇓⇓–15).
DksA binds to RNAP transcription initiation complexes and is implicated in the stringent response, which is a cellular response to environmental stresses such as amino acid, carbon, phosphate, iron, and lipid limitation, as well as temperature and oxidative stress (8, 9). The hallmark of this response is accumulation of guanosine tetraphosphate and guanosine pentaphosphate [(p)ppGpp]. These molecules directly interact with Escherichia coli RNAP and limit the ribosomal RNA and tRNA synthesis while switching on the transcription of many survival genes such as amino acid biosynthesis genes (9⇓⇓⇓⇓⇓–15).
Henard et al. (7) had shown that DksA from Salmonella can be oxidized by NO or H2O …
[↵][1]1To whom correspondence should be addressed. Email: cashelm{at}mail.nih.gov.
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Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2902148484